Dan Merenstein, MD

How do FPs compare with dermatologists?

Dermatology literature boasts about the superiority of the dermatologist in diagnostic ability, cost savings, and cancer prevention when compared with primary care physicians.^6-10 Studies have evaluated the skill level of primary care physicians compared with dermatologists in identifying skin disorders when tested with color transparencies, computer images, and slides—however, rarely with actual patients.^7,9-16 Some studies have suggested a higher rate of referral for skin problems than for other non-dermatologic conditions.^14,17,18

Often the outcome of interest in these studies is disease-oriented, judging a physician’s diagnostic ability, rather than examining a patient-oriented outcome, such as resolution of lesion or patient satisfaction.

Thus, the secondary aims of our study were to observe how family physicians diagnose and treat the lesions, and to gauge their concordance with dermatologists’ assessments and plans. We hypothesized that, in an office setting, family physicians would provide effective and efficient treatment for most patients who present with new skin lesions, and that there is high diagnostic concordance between the 2 specialties.

We first share our study findings, and then provide details of our Methodology and Results.

Family physicians excel at dermatologic care

Our study demonstrates that most skin conditions diagnosed and managed by family physicians improve. At day 7, 84% of patients who were contacted reported their skin lesions were “better” or “much better.” Moreover, patients said they were highly satisfied with their care. Referrals to subspecialists were infrequent.

These findings counter those from previous studies questioning primary care physicians’ care of dermatologic conditions. We believe it is likely that patients in previous studies reflected different populations than are typically seen by family physicians.^18-20 Another difference may be that family physicians used other resources to assist with their diagnosis and treatment decisions. As we hypothesized, family physicians had good correlation with dermatologists in both diagnosis and treatment, and skin lesions improved.

Important study limitations

We relied on patient reports of improvement. While-self impression of degree of improvement is a patient-centered outcome, there may be instances in which inappropriate or insufficient treatment may produce temporary symptomatic relief and mask true improvement.

Although the patients’ primary care physicians were not involved in the follow-up process, it is possible they felt some social pressure to report higher levels of improvement or satisfaction.

Though we attempted to enroll all eligible patients, some patients seen for skin conditions may not have been captured. As we met our planned enrollment rates, we believe we captured most of the eligible encounters.

Some studies have questioned primary care physicians’ abilities to properly diagnose skin cancers.^21,22 Our study was not designed or powered to detect skin cancers or the number, if any, of missed diagnoses of skin cancer.

Cues for teachers of family medicine

Most diagnoses fell within a limited set of diagnostic categories that probably reflect a distribution of skin disorders more typical within family medicine than in dermatology clinics. This range of disease defines a set of diagnostic skills, information resources, and treatment plans required to make these diagnoses and manage these conditions in family practice settings. This information should help physicians involved in training family physicians to concentrate on these common categories of diagnoses. Most important, our study conducted with actual patients found that family physicians manage skin lesions effectively and efficiently, with high patient satisfaction.

Methods

Study design and participants

We conducted a multisite, 3-state (Maryland, Virginia, and Washington, DC) prospective cohort study under the auspices of the Capital Area Practice Based Research Network (CAPRICORN). Between May 24 and August 13, 2004, all patients with new skin lesions who were seen by participating physicians were expected to enter into the study. Institutional Review Board approval was obtained from Georgetown University prior to the study. Written informed consent was obtained from all physicians and patients.

Inclusion/exclusion criteria

A lesion was considered new if patients presented to a family physician with one or more skin lesion that had not been previously treated or examined by another physician.

Patients were ineligible if they: 1) had a lesion with unknown duration; 2) had no telephone for follow-up; 3) did not speak English or Spanish; or, 4) had a lesion resulting from trauma.

Interventions

The initial intervention consisted of 2 parts: 1) after examining a patient, family physicians completed a 10-question survey, recording diagnosis, treatment plan, and resources used in treatment; 2) research assistants completed a 14-question survey, consisting of general patient and lesion information. Follow-up patient surveys were completed by telephone on days 7, 28, and 84.

Two university-based dermatologists helped develop the photography protocol. They specifically requested 3 digital photos of lesions under incandescent light, specific information for diagnosis, and direction for how photographs should be taken. The photographs were taken using Olympus C-5000 5MP Digital Camera w/3x Optical Zoom and were developed with HP photo glossy paper. The dermatologists separately reviewed the photographs blinded to the family physician’s diagnosis and treatment. The dermatologists commented on diagnosis and treatment plan for the first 99 patients enrolled in the study.

Outcomes

The primary outcome was dichotomous: whether skin lesions improved or not at day 7. Secondary outcomes were measures of improvement at days 28 and 84. We also examined patients’ satisfaction on a scale of 1 to 5 (“How satisfied were you with your skin care provided by your family physician?” 1=very satisfied, 5=very unsatisfied).

The categorization of acute skin lesions was developed by a modified delphi process in order to classify the lesions into groups. The principal investigator initially categorized all diagnoses and treatments. Next, 3 other members of the study (AK, BP, and DM) individually reviewed and guided categorizations. The 2 dermatologists gave the final input. This resulted in 41 categories for diagnosis and 9 for treatment.

Statistical analysis

Descriptive statistics provided baseline characteristics for the group. Frequencies were computed on patient, visit, and lesion characteristics, including patient improvement at days 7, 28, and 84. We also computed patient satisfaction with the care provided by their physician at 7, 28, and 84 days. Agreement rates between the family physicians and the 2 dermatologists were obtained for the subset of cases where both dermatologists agreed on the diagnosis. Similarly, the agreement rates were computed for recommended treatment using only those cases where the 2 dermatologists agreed on treatment. All descriptive statistics were computed with SPSS (SPSS, Inc, Chicago, Ill).

RESULTS

A total of 244 patients with 267 skin lesions were recruited by 53 family physicians during the study period. The 7-day follow-up patient survey was completed for 234 lesions (88%), the 28-day survey was completed for 220 lesions (82%), and the 84-day survey was completed for 203 lesions (76%). Study participants ranged in age from 3 months to 86 years; adults were predominantly college-educated, non-Hispanic, and white (TABLE 1). The majority of study participants (73%) reported that their skin lesion was the primary reason for their appointment.

Characteristics of the clinical encounters are presented in TABLE 2. While most skin lesions were present for 30 days or less (62%), over one quarter had been present for more than 90 days. The family physicians made 40 general dermatologic diagnoses. Only 3 lesions (1%) were considered malignant (data not shown). Family physicians reported relatively high confidence with their diagnoses (mean confidence score of 8.4, with range 1 to 10, 1=not at all certain, 10=very certain).

Other characteristics of the clinical encounters not shown in TABLE 2 are the family physicians’ judgment on resolution of the lesions and diagnostic steps used in treating the lesions. In most cases, family physicians believed the lesion would resolve within 12 weeks (203 lesions received a score of ≥7, 0=no improvement expected, 10=complete resolution expected). There was a bimodal distribution with 144 lesions receiving a 10, while 36 received a grade of 0. To make their diagnosis, most family physicians examined other parts of the skin (70%), consulted a colleague (14%), or consulted an electronic resource (6%). Laboratory tests, skin scrapings, diagnostic cultures, Woods lamp exams, or skin biopsies were performed in a total of 10% of encounters.

TABLE 3 reports the primary outcome, patient-reported resolution of skin lesions. These data were restricted only to lesions that were expected to improve (defined as a clinician assigned resolution score ≥7).

Overall, patients were very satisfied with the dermatologic care provided by their family physician. On a 5-point satisfaction scale, 55% of patients reported 1, the highest satisfaction level and 34% reported 2, the next highest level at day 7. At days 28 and 84, 93% of the patients reported the 2 highest levels of satisfaction. These data exclude patients lost to follow-up. Including all participants in the denominator, the rates of either the 2 highest levels of satisfaction at day 7 was 78%, at day 28 was 76%, and at day 84 was 70%.

The overall agreements in diagnosis and treatment, respectively, between the family physicians and the dermatologists were 72% and 80%. We examined only the aspects where both of the dermatologists agreed. Interestingly, for the more common diagnoses, the agreement rates were above 80%; however, for less common diagnoses, the rates were 62%. This trend was not observed in the treatment agreements, primarily due to dermatologists recommending steroids much more often than family physicians prescribed steroids. See Table 4 and Table 5.

TABLE 1
Characteristics of study sample

TABLE 2
Skin lesions seen in study sites

TABLE 3
Patients reported high satisfaction

Acknowledgments

The views expressed are those of the authors. No official endorsement by the Agency for Healthcare Research and Quality is intended or should be inferred. We would like to thank the following medical students who played an integral role in recruitment, Aaron Baker, Richard Sisson and Giovina Lara Bomba. We would like to thank Haewon Park for editorial assistance. We would like to that the following practices for participation, Potomac Physician Associates of Kensington, La Clinica del Pueblo, Community of Hope, Fort Lincoln, Fairfax Family Practice of Vienna, Fair Oaks, and Prince William.

CORRESPONDENCE
Dan Merenstein, MD, 215 Kober Cogan Hall, 3750 Reservoir Road, NW, Washington, DC 20007. E-mail: djm23@georgetown.edu

How do FPs compare with dermatologists?

Dermatology literature boasts about the superiority of the dermatologist in diagnostic ability, cost savings, and cancer prevention when compared with primary care physicians.^6-10 Studies have evaluated the skill level of primary care physicians compared with dermatologists in identifying skin disorders when tested with color transparencies, computer images, and slides—however, rarely with actual patients.^7,9-16 Some studies have suggested a higher rate of referral for skin problems than for other non-dermatologic conditions.^14,17,18

Often the outcome of interest in these studies is disease-oriented, judging a physician’s diagnostic ability, rather than examining a patient-oriented outcome, such as resolution of lesion or patient satisfaction.

Thus, the secondary aims of our study were to observe how family physicians diagnose and treat the lesions, and to gauge their concordance with dermatologists’ assessments and plans. We hypothesized that, in an office setting, family physicians would provide effective and efficient treatment for most patients who present with new skin lesions, and that there is high diagnostic concordance between the 2 specialties.

We first share our study findings, and then provide details of our Methodology and Results.

Family physicians excel at dermatologic care

Our study demonstrates that most skin conditions diagnosed and managed by family physicians improve. At day 7, 84% of patients who were contacted reported their skin lesions were “better” or “much better.” Moreover, patients said they were highly satisfied with their care. Referrals to subspecialists were infrequent.

These findings counter those from previous studies questioning primary care physicians’ care of dermatologic conditions. We believe it is likely that patients in previous studies reflected different populations than are typically seen by family physicians.^18-20 Another difference may be that family physicians used other resources to assist with their diagnosis and treatment decisions. As we hypothesized, family physicians had good correlation with dermatologists in both diagnosis and treatment, and skin lesions improved.

Important study limitations

We relied on patient reports of improvement. While-self impression of degree of improvement is a patient-centered outcome, there may be instances in which inappropriate or insufficient treatment may produce temporary symptomatic relief and mask true improvement.

Although the patients’ primary care physicians were not involved in the follow-up process, it is possible they felt some social pressure to report higher levels of improvement or satisfaction.

Though we attempted to enroll all eligible patients, some patients seen for skin conditions may not have been captured. As we met our planned enrollment rates, we believe we captured most of the eligible encounters.

Some studies have questioned primary care physicians’ abilities to properly diagnose skin cancers.^21,22 Our study was not designed or powered to detect skin cancers or the number, if any, of missed diagnoses of skin cancer.

Cues for teachers of family medicine

Most diagnoses fell within a limited set of diagnostic categories that probably reflect a distribution of skin disorders more typical within family medicine than in dermatology clinics. This range of disease defines a set of diagnostic skills, information resources, and treatment plans required to make these diagnoses and manage these conditions in family practice settings. This information should help physicians involved in training family physicians to concentrate on these common categories of diagnoses. Most important, our study conducted with actual patients found that family physicians manage skin lesions effectively and efficiently, with high patient satisfaction.

Methods

Study design and participants

We conducted a multisite, 3-state (Maryland, Virginia, and Washington, DC) prospective cohort study under the auspices of the Capital Area Practice Based Research Network (CAPRICORN). Between May 24 and August 13, 2004, all patients with new skin lesions who were seen by participating physicians were expected to enter into the study. Institutional Review Board approval was obtained from Georgetown University prior to the study. Written informed consent was obtained from all physicians and patients.

Inclusion/exclusion criteria

A lesion was considered new if patients presented to a family physician with one or more skin lesion that had not been previously treated or examined by another physician.

Patients were ineligible if they: 1) had a lesion with unknown duration; 2) had no telephone for follow-up; 3) did not speak English or Spanish; or, 4) had a lesion resulting from trauma.

Interventions

The initial intervention consisted of 2 parts: 1) after examining a patient, family physicians completed a 10-question survey, recording diagnosis, treatment plan, and resources used in treatment; 2) research assistants completed a 14-question survey, consisting of general patient and lesion information. Follow-up patient surveys were completed by telephone on days 7, 28, and 84.

Two university-based dermatologists helped develop the photography protocol. They specifically requested 3 digital photos of lesions under incandescent light, specific information for diagnosis, and direction for how photographs should be taken. The photographs were taken using Olympus C-5000 5MP Digital Camera w/3x Optical Zoom and were developed with HP photo glossy paper. The dermatologists separately reviewed the photographs blinded to the family physician’s diagnosis and treatment. The dermatologists commented on diagnosis and treatment plan for the first 99 patients enrolled in the study.

Outcomes

The primary outcome was dichotomous: whether skin lesions improved or not at day 7. Secondary outcomes were measures of improvement at days 28 and 84. We also examined patients’ satisfaction on a scale of 1 to 5 (“How satisfied were you with your skin care provided by your family physician?” 1=very satisfied, 5=very unsatisfied).

The categorization of acute skin lesions was developed by a modified delphi process in order to classify the lesions into groups. The principal investigator initially categorized all diagnoses and treatments. Next, 3 other members of the study (AK, BP, and DM) individually reviewed and guided categorizations. The 2 dermatologists gave the final input. This resulted in 41 categories for diagnosis and 9 for treatment.

Statistical analysis

Descriptive statistics provided baseline characteristics for the group. Frequencies were computed on patient, visit, and lesion characteristics, including patient improvement at days 7, 28, and 84. We also computed patient satisfaction with the care provided by their physician at 7, 28, and 84 days. Agreement rates between the family physicians and the 2 dermatologists were obtained for the subset of cases where both dermatologists agreed on the diagnosis. Similarly, the agreement rates were computed for recommended treatment using only those cases where the 2 dermatologists agreed on treatment. All descriptive statistics were computed with SPSS (SPSS, Inc, Chicago, Ill).

RESULTS

A total of 244 patients with 267 skin lesions were recruited by 53 family physicians during the study period. The 7-day follow-up patient survey was completed for 234 lesions (88%), the 28-day survey was completed for 220 lesions (82%), and the 84-day survey was completed for 203 lesions (76%). Study participants ranged in age from 3 months to 86 years; adults were predominantly college-educated, non-Hispanic, and white (TABLE 1). The majority of study participants (73%) reported that their skin lesion was the primary reason for their appointment.

Characteristics of the clinical encounters are presented in TABLE 2. While most skin lesions were present for 30 days or less (62%), over one quarter had been present for more than 90 days. The family physicians made 40 general dermatologic diagnoses. Only 3 lesions (1%) were considered malignant (data not shown). Family physicians reported relatively high confidence with their diagnoses (mean confidence score of 8.4, with range 1 to 10, 1=not at all certain, 10=very certain).

Other characteristics of the clinical encounters not shown in TABLE 2 are the family physicians’ judgment on resolution of the lesions and diagnostic steps used in treating the lesions. In most cases, family physicians believed the lesion would resolve within 12 weeks (203 lesions received a score of ≥7, 0=no improvement expected, 10=complete resolution expected). There was a bimodal distribution with 144 lesions receiving a 10, while 36 received a grade of 0. To make their diagnosis, most family physicians examined other parts of the skin (70%), consulted a colleague (14%), or consulted an electronic resource (6%). Laboratory tests, skin scrapings, diagnostic cultures, Woods lamp exams, or skin biopsies were performed in a total of 10% of encounters.

TABLE 3 reports the primary outcome, patient-reported resolution of skin lesions. These data were restricted only to lesions that were expected to improve (defined as a clinician assigned resolution score ≥7).

Overall, patients were very satisfied with the dermatologic care provided by their family physician. On a 5-point satisfaction scale, 55% of patients reported 1, the highest satisfaction level and 34% reported 2, the next highest level at day 7. At days 28 and 84, 93% of the patients reported the 2 highest levels of satisfaction. These data exclude patients lost to follow-up. Including all participants in the denominator, the rates of either the 2 highest levels of satisfaction at day 7 was 78%, at day 28 was 76%, and at day 84 was 70%.

The overall agreements in diagnosis and treatment, respectively, between the family physicians and the dermatologists were 72% and 80%. We examined only the aspects where both of the dermatologists agreed. Interestingly, for the more common diagnoses, the agreement rates were above 80%; however, for less common diagnoses, the rates were 62%. This trend was not observed in the treatment agreements, primarily due to dermatologists recommending steroids much more often than family physicians prescribed steroids. See Table 4 and Table 5.

TABLE 1
Characteristics of study sample

TABLE 2
Skin lesions seen in study sites

TABLE 3
Patients reported high satisfaction

Acknowledgments

The views expressed are those of the authors. No official endorsement by the Agency for Healthcare Research and Quality is intended or should be inferred. We would like to thank the following medical students who played an integral role in recruitment, Aaron Baker, Richard Sisson and Giovina Lara Bomba. We would like to thank Haewon Park for editorial assistance. We would like to that the following practices for participation, Potomac Physician Associates of Kensington, La Clinica del Pueblo, Community of Hope, Fort Lincoln, Fairfax Family Practice of Vienna, Fair Oaks, and Prince William.

CORRESPONDENCE
Dan Merenstein, MD, 215 Kober Cogan Hall, 3750 Reservoir Road, NW, Washington, DC 20007. E-mail: djm23@georgetown.edu

How do FPs compare with dermatologists?

Dermatology literature boasts about the superiority of the dermatologist in diagnostic ability, cost savings, and cancer prevention when compared with primary care physicians.^6-10 Studies have evaluated the skill level of primary care physicians compared with dermatologists in identifying skin disorders when tested with color transparencies, computer images, and slides—however, rarely with actual patients.^7,9-16 Some studies have suggested a higher rate of referral for skin problems than for other non-dermatologic conditions.^14,17,18

Often the outcome of interest in these studies is disease-oriented, judging a physician’s diagnostic ability, rather than examining a patient-oriented outcome, such as resolution of lesion or patient satisfaction.

Thus, the secondary aims of our study were to observe how family physicians diagnose and treat the lesions, and to gauge their concordance with dermatologists’ assessments and plans. We hypothesized that, in an office setting, family physicians would provide effective and efficient treatment for most patients who present with new skin lesions, and that there is high diagnostic concordance between the 2 specialties.

We first share our study findings, and then provide details of our Methodology and Results.

Family physicians excel at dermatologic care

Our study demonstrates that most skin conditions diagnosed and managed by family physicians improve. At day 7, 84% of patients who were contacted reported their skin lesions were “better” or “much better.” Moreover, patients said they were highly satisfied with their care. Referrals to subspecialists were infrequent.

These findings counter those from previous studies questioning primary care physicians’ care of dermatologic conditions. We believe it is likely that patients in previous studies reflected different populations than are typically seen by family physicians.^18-20 Another difference may be that family physicians used other resources to assist with their diagnosis and treatment decisions. As we hypothesized, family physicians had good correlation with dermatologists in both diagnosis and treatment, and skin lesions improved.

Important study limitations

We relied on patient reports of improvement. While-self impression of degree of improvement is a patient-centered outcome, there may be instances in which inappropriate or insufficient treatment may produce temporary symptomatic relief and mask true improvement.

Although the patients’ primary care physicians were not involved in the follow-up process, it is possible they felt some social pressure to report higher levels of improvement or satisfaction.

Though we attempted to enroll all eligible patients, some patients seen for skin conditions may not have been captured. As we met our planned enrollment rates, we believe we captured most of the eligible encounters.

Some studies have questioned primary care physicians’ abilities to properly diagnose skin cancers.^21,22 Our study was not designed or powered to detect skin cancers or the number, if any, of missed diagnoses of skin cancer.

Cues for teachers of family medicine

Most diagnoses fell within a limited set of diagnostic categories that probably reflect a distribution of skin disorders more typical within family medicine than in dermatology clinics. This range of disease defines a set of diagnostic skills, information resources, and treatment plans required to make these diagnoses and manage these conditions in family practice settings. This information should help physicians involved in training family physicians to concentrate on these common categories of diagnoses. Most important, our study conducted with actual patients found that family physicians manage skin lesions effectively and efficiently, with high patient satisfaction.

Methods

Study design and participants

We conducted a multisite, 3-state (Maryland, Virginia, and Washington, DC) prospective cohort study under the auspices of the Capital Area Practice Based Research Network (CAPRICORN). Between May 24 and August 13, 2004, all patients with new skin lesions who were seen by participating physicians were expected to enter into the study. Institutional Review Board approval was obtained from Georgetown University prior to the study. Written informed consent was obtained from all physicians and patients.

Inclusion/exclusion criteria

A lesion was considered new if patients presented to a family physician with one or more skin lesion that had not been previously treated or examined by another physician.

Patients were ineligible if they: 1) had a lesion with unknown duration; 2) had no telephone for follow-up; 3) did not speak English or Spanish; or, 4) had a lesion resulting from trauma.

Interventions

The initial intervention consisted of 2 parts: 1) after examining a patient, family physicians completed a 10-question survey, recording diagnosis, treatment plan, and resources used in treatment; 2) research assistants completed a 14-question survey, consisting of general patient and lesion information. Follow-up patient surveys were completed by telephone on days 7, 28, and 84.

Two university-based dermatologists helped develop the photography protocol. They specifically requested 3 digital photos of lesions under incandescent light, specific information for diagnosis, and direction for how photographs should be taken. The photographs were taken using Olympus C-5000 5MP Digital Camera w/3x Optical Zoom and were developed with HP photo glossy paper. The dermatologists separately reviewed the photographs blinded to the family physician’s diagnosis and treatment. The dermatologists commented on diagnosis and treatment plan for the first 99 patients enrolled in the study.

Outcomes

The primary outcome was dichotomous: whether skin lesions improved or not at day 7. Secondary outcomes were measures of improvement at days 28 and 84. We also examined patients’ satisfaction on a scale of 1 to 5 (“How satisfied were you with your skin care provided by your family physician?” 1=very satisfied, 5=very unsatisfied).

The categorization of acute skin lesions was developed by a modified delphi process in order to classify the lesions into groups. The principal investigator initially categorized all diagnoses and treatments. Next, 3 other members of the study (AK, BP, and DM) individually reviewed and guided categorizations. The 2 dermatologists gave the final input. This resulted in 41 categories for diagnosis and 9 for treatment.

Statistical analysis

Descriptive statistics provided baseline characteristics for the group. Frequencies were computed on patient, visit, and lesion characteristics, including patient improvement at days 7, 28, and 84. We also computed patient satisfaction with the care provided by their physician at 7, 28, and 84 days. Agreement rates between the family physicians and the 2 dermatologists were obtained for the subset of cases where both dermatologists agreed on the diagnosis. Similarly, the agreement rates were computed for recommended treatment using only those cases where the 2 dermatologists agreed on treatment. All descriptive statistics were computed with SPSS (SPSS, Inc, Chicago, Ill).

RESULTS

A total of 244 patients with 267 skin lesions were recruited by 53 family physicians during the study period. The 7-day follow-up patient survey was completed for 234 lesions (88%), the 28-day survey was completed for 220 lesions (82%), and the 84-day survey was completed for 203 lesions (76%). Study participants ranged in age from 3 months to 86 years; adults were predominantly college-educated, non-Hispanic, and white (TABLE 1). The majority of study participants (73%) reported that their skin lesion was the primary reason for their appointment.

Characteristics of the clinical encounters are presented in TABLE 2. While most skin lesions were present for 30 days or less (62%), over one quarter had been present for more than 90 days. The family physicians made 40 general dermatologic diagnoses. Only 3 lesions (1%) were considered malignant (data not shown). Family physicians reported relatively high confidence with their diagnoses (mean confidence score of 8.4, with range 1 to 10, 1=not at all certain, 10=very certain).

Other characteristics of the clinical encounters not shown in TABLE 2 are the family physicians’ judgment on resolution of the lesions and diagnostic steps used in treating the lesions. In most cases, family physicians believed the lesion would resolve within 12 weeks (203 lesions received a score of ≥7, 0=no improvement expected, 10=complete resolution expected). There was a bimodal distribution with 144 lesions receiving a 10, while 36 received a grade of 0. To make their diagnosis, most family physicians examined other parts of the skin (70%), consulted a colleague (14%), or consulted an electronic resource (6%). Laboratory tests, skin scrapings, diagnostic cultures, Woods lamp exams, or skin biopsies were performed in a total of 10% of encounters.

TABLE 3 reports the primary outcome, patient-reported resolution of skin lesions. These data were restricted only to lesions that were expected to improve (defined as a clinician assigned resolution score ≥7).

Overall, patients were very satisfied with the dermatologic care provided by their family physician. On a 5-point satisfaction scale, 55% of patients reported 1, the highest satisfaction level and 34% reported 2, the next highest level at day 7. At days 28 and 84, 93% of the patients reported the 2 highest levels of satisfaction. These data exclude patients lost to follow-up. Including all participants in the denominator, the rates of either the 2 highest levels of satisfaction at day 7 was 78%, at day 28 was 76%, and at day 84 was 70%.

The overall agreements in diagnosis and treatment, respectively, between the family physicians and the dermatologists were 72% and 80%. We examined only the aspects where both of the dermatologists agreed. Interestingly, for the more common diagnoses, the agreement rates were above 80%; however, for less common diagnoses, the rates were 62%. This trend was not observed in the treatment agreements, primarily due to dermatologists recommending steroids much more often than family physicians prescribed steroids. See Table 4 and Table 5.

TABLE 1
Characteristics of study sample

TABLE 2
Skin lesions seen in study sites

TABLE 3
Patients reported high satisfaction

Acknowledgments

The views expressed are those of the authors. No official endorsement by the Agency for Healthcare Research and Quality is intended or should be inferred. We would like to thank the following medical students who played an integral role in recruitment, Aaron Baker, Richard Sisson and Giovina Lara Bomba. We would like to thank Haewon Park for editorial assistance. We would like to that the following practices for participation, Potomac Physician Associates of Kensington, La Clinica del Pueblo, Community of Hope, Fort Lincoln, Fairfax Family Practice of Vienna, Fair Oaks, and Prince William.

CORRESPONDENCE
Dan Merenstein, MD, 215 Kober Cogan Hall, 3750 Reservoir Road, NW, Washington, DC 20007. E-mail: djm23@georgetown.edu

It is estimated that adults have 2 to 3 colds a year, of which just 0.5% to 2% are complicated by bacterial sinusitis. However, primary care physicians treat over half of these colds with antibiotics.¹ Sinusitis is the fifth most common diagnosis for which antibiotics are prescribed in the outpatient setting, with more than $6 billion spent annually in the United States on prescription and over-the-counter medications.^1-3 Can we know with greater certainty when antibiotics are indicated for sinusitis?

A meta-analysis of randomized controlled studies has shown that the likelihood of bacterial sinusitis is increased (sensitivity 76%, specificity 79%) and antibiotics are helpful when a patient exhibits at least 3 of 4 cardinal clinical features: 1) purulent nasal discharge predominating on one side; 2) local facial pain predominating on one side; 3) purulent nasal discharge on both sides; and 4) pus in the nasal cavity.² Although use of these criteria is encouraged, they are based on studies that recruited patients from subspecialty clinics and measured disease-oriented outcomes such as findings on sinus radiographs, CT scans, and sinus puncture with culture.^4-12 Most cases of sinusitis, however, are treated in primary care settings where measuring such outcomes is impractical.

Given the lack of epidemiologic evidence as to which patients would benefit from treatment of sinusitis, primary care physicians face the dilemma of deciding during office encounters which patients should receive antibiotics and which have a viral infection for which symptomatic treatment is indicated.¹³

Our goal was to study the type of patient for whom this dilemma arises and to use clinical improvement as our primary outcome. We randomly assigned patients presenting with sinusitis complaints to receive amoxicillin or placebo, and compared the rates of improvement, time to improvement, and patient’s self-rating of sickness at the end of 2 weeks. We also tested the clinical prediction rule to see if participants with 3 or 4 signs and symptoms had different clinical outcomes than the others.

Methods

Setting

We conducted a randomized double-blind clinical trial of amoxicillin vs placebo. All patients were recruited from a suburban primary care office. Two physicians and one nurse practitioner enrolled and treated all patients over an 18-month period (Oct 1, 2001 to March 31, 2003). The clinicians involved in the study were trained to identify purulent discharge in the nasal cavity. Institutional Review Board approval was obtained from Georgetown University prior to the study. Written informed consent was obtained from all participating patients.

Patients

Patients were eligible to participate if they were 18 years or older; had at least 1 cardinal feature described by the clinical prediction rule: 1) purulent nasal discharge predominating on one side, 2) local facial pain predominating on one side, 3) purulent nasal discharge on both sides, or 4) pus in the nasal cavity; and had symptoms for at least 7 days. Patients were excluded if their histories included antibiotic treatment within the past month, allergy to penicillin, sinus surgery, compromised immunity, pneumonia, or streptococcal pharyngitis.

Randomization

Permuted block randomization stratified for the 3 participating clinicians was used to determine treatment assignment. Patients were given an envelope containing 40 capsules, either a placebo medicine taken twice daily for 10 days or 1000 mg of amoxicillin (500 mg pills) taken twice daily for 10 days. The envelopes were opaque, and each had 40 identical-appearing pills (to ensure allocation concealment). The participating clinicians were naive to the treatment assignments.

Assessment of outcomes

Trained personnel, masked to treatment assignment, conducted follow-up telephone interviews on days 3, 7, and 14 following patients’ visits for sinusitis, to assess clinical improvement. Twelve follow-up questions were asked.

Sample size

The primary outcome used to determine sample size was dichotomous—either “improved” or “not improved” by the end of 2 weeks. Thus, patients were asked, “what day were you entirely improved.” The sample sizes obtained per group (67 for amoxicillin and 68 for placebo) provided 80% power for detecting a change of 25% in rates of improvement.

Statistical analysis

Basic descriptive statistics were used to describe the groups. Baseline characteristics were compared between the 2 groups using chi-square test and Fisher’s exact test for categorical variables. For continuous variables, the Student’s t-test was used; the Wilcoxon Rank Sum test was used for ordinal or skewed variables. Similar statistical tests were used to compare baseline characteristics between the providers and also at the conclusion of the study between the responders for each group.

For the outcome variables, we hypothesized no difference between the groups either in the rates of improvement, times to improvement, or in patients’ self-rating of sickness. The actual proportions improving between the 2 groups were compared using the chi-square test. Relative risk estimates and 95% confidence intervals were calculated to provide measures of risk and precision. Multiple logistic regression was used to compare the rates of improvement adjusting for the number of signs or symptoms classified as either 1, 2, or 3–4, obtained from the clinical prediction rule (Table 1).

The Kaplan-Meier method was used to construct the curves showing the time until patient improvement for each treatment group. The Wilcoxon test was then used to test the statistical significance in these curves (Figure). Cox’s Proportional Hazards regression was used to test for differences in the time to improvement between the groups adjusting for the number of signs or symptoms.

Additionally, a univariate repeated measures analysis of variance model was constructed to compare the 10-point Likert scale scores for the question, “How sick do you feel today?” In this model, the number of signs and symptoms was entered as a covariate in the analysis. Orthogonal contrasts were used as post-hoc tests to compare the difference between the groups within each time point (Table 2 ).

For the subgroup of patients who improved, analysis of covariance was used to compare the mean number of days to improvement between the groups. In this case the number of signs and symptoms was used as the covariate (Table 3). The Kaplan-Meier method and the Wilcoxon test were used to compare the cumulative rates of improvement (Figure). Unadjusted P-values are reported.

Primary analyses were performed using the intention-to-treat principle. All statistical analyses were performed using JMP Software (Product of SAS Institute Inc, Cary, NC). Statistical significance was set at 0.05 and exact P-values are reported.

TABLE 1
Baseline characteristics for amoxicillin and placebo groups

Figure
Kaplan-Meier curve for improvement—amoxicillin (n=67) vs placebo (n=68)*

TABLE 2
Comparison of mean Likert scores by group across follow-up time points Question asked at each time point:

TABLE 3
Mean number of days to improvement by group and number of signs and symptoms (at baseline) for patients who improved

Results

During the 18-month enrollment period, the 3 providers recorded all patients aged >18 years who had at least 1 cardinal feature described by the clinical prediction rule and had symptoms for a minimum of 7 days. Thus, initially 308 patients were approached for enrollment; 173 patients did not qualify after the exclusion criteria were applied, leaving 135 patients for randomization. Sixty-seven received amoxicillin and 68 received placebo. For 11 patients in the amoxicillin arm and 8 in the placebo arm, only baseline data were collected. These patients were then considered as lost to follow-up and were counted as “not improved” in the intention-to-treat analysis.

There were no significant differences (P >.05) in baseline characteristics of the treatment groups (Table 1). Additionally, there were no significant differences in the baseline characteristics between the providers (data not shown).

In the amoxicillin group 32 (48%) had completely improved compared with 25 (37%) in the placebo group (P=.26) after 2 weeks (relative risk of treatment failure=1.3; 95% CI, 0.87–1.94). However, individuals in the amoxicillin group did improve significantly earlier, as the Kaplan-Meier curve demonstrates (Figure). The first person in the amoxicillin group improved on day 3, compared with day 7 in the placebo group. This earlier improvement continued throughout the study (P=.039).

Subgroup analysis of the 57 who demonstrated complete recovery shows the amoxicillin group improved earlier as does the Kaplan-Meier curves in the Figure. In the amoxicillin group, the median day to any improvement was day 8 compared with day 12 for the placebo group (P=.005), while the mean day to improvement for the amoxicillin group was 8.1 days vs 10.7 days for placebo group.

When patients were asked “How sick do you feel today,” the average Likert scores decreased from 6. 1 (day 0) to 2.3 (day 14), and 6.3 (day 0) to 2.8 (day 14), in the amoxicillin and placebo groups, respectively. At each time point, there were no significant clinical or statistical differences between the 2 groups in how they rated their improvement (Table 2). Furthermore, examining only those who reported total improvement within 14 days showed no differences among groups.

No statistically significant differences were observed between the treatment groups that entailed the clinical prediction rule. However, in the patients who were improved at 14 days, the average number of days to improvement was consistently between 2 to 2.5 days shorter in the amoxicillin group compared with placebo (Table 3).

Side effects

No patients dropped out of the study due to adverse side effects (Table 4). There were no serious or unexpected side effects, with the majority related to gastrointestinal problems, such as diarrhea and abdominal pain.

TABLE 4
A Frequency of reported side effects by group

Discussion

With respect to the patient-oriented outcome of clinical improvement, amoxicillin provided no significant benefit over placebo in the treatment of patients presenting with sinusitis complaints. On average our patients who had symptoms for 11 days prior to enrollment and are typical of patients that are often recommended for treatment with antibiotics.^14,15

Our findings are consistent with others in which the overall benefit of antibiotics was minimal or nonexistent.^16,18 But among individuals who did improve, those who received amoxicillin improved much earlier, both clinically and statistically. Unfortunately we were not able to specify those who are likely to improve. Clearly, further patient-oriented outcome studies are needed to help primary care physicians decide which patients may benefit from antibiotic treatment.

Antibiotics have not been shown to prevent the sequelae of acute sinusitis. One of the major difficulties in treating sinusitis is the lack of agreement about which outcomes are desired.^19,20 Nearly 66% of patients diagnosed with sinusitis will get better without treatment, though nearly two thirds of patients will continue to have such symptoms as cough and nasal discharge for up to 3 weeks.^21,22 Thus, we believe that to give antibiotics only to individuals who would truly benefit from them, policy makers, primary care physicians, and patients need to reassess clinically what constitutes sinusitis, and what outcomes are most desired. If the goal is to cure purulent nasal discharge, we are likely over-treating with antibiotics; as our study showed, after 2 weeks most patients in both groups still had nasal symptoms.

Our pilot of the clinical prediction rule failed to predict a proper response to antibiotics or the time to improvement. Although our numbers were not large, no trend was observed towards improvement in individuals with a higher score on the clinical prediction rule.

Our study has some important limitations. Interestingly we found different results when we used the dichotomous outcome of totally improved versus the 10-point Likert scale. A priori we decided our primary outcome was the dichotomous improvement, but which measure is more important and should be used is open to varying interpretations. Additionally, our study office unexpectedly closed and thus we could not recruit the number of patients we initially had planned. This limited our power to find differences between groups based on the number of cardinal clinical features. We encountered noncompliance with follow-up, as expected with the study design. We also arbitrarily stopped follow-up at 14 days, and cases that had not entirely improved were considered clinical failures in all but the Likert scale analysis. It is possible our results may have differed if we had continued to follow patients at 21 or 28 days, or if we had conducted the study at more than one office.

Methodologically, we conducted a rigorous study and showed that patients diagnosed with clinical sinusitis fared no better with amoxicillin or placebo, when measuring the patient-oriented outcome of complete improvement. But a subgroup of patients who were given antibiotics did improve at a much quicker rate. The difficulty is in clinically identifying this group and treating them with antibiotics. Conversely, using antibiotics in patients unnecessarily would only cause potential individual and societal harm. More clinically oriented studies need to be conducted to address this issue and elucidate what signs and symptoms these patients exhibit, to help clarify who should be treated with antibiotics.

ACKNOWLEDGMENTS

When this article was prepared, Dan Merenstein was an assistant professor of Family Medicine and Pediatrics at Georgetown University. This study was part of the Capricorn Research Network of Georgetown University. This projectwas supported by a grant from the American Academy ofFamily Physicians and the American Academy of FamilyPhysicians Foundation “Joint AAFP/F-AAFP Grant AwardsProgram” (JGAP). Support was also provided by the CapitolArea Primary Care Research Network. Research presentedat NAPRCG 2003, Banff, Canada.

We thank Joel Merenstein for insightful feedback and intelligent comments about study design and input with manuscript. We thank Goutham Rao and Traci Reisner for editorial help. We thank Community Drug Compounding Center of Pittsburgh and pharmacist Susan Freedenberg for drug development.

Corresponding author
Dan Merenstein, MD, Robert Wood Johnson Clinical Scholar, The Johns Hopkins Hospital, 600 North Wolfe St., Carnegie 291, Baltimore, MD 21287-6220. E-mail: dmerenstein@jhu.edu.

It is estimated that adults have 2 to 3 colds a year, of which just 0.5% to 2% are complicated by bacterial sinusitis. However, primary care physicians treat over half of these colds with antibiotics.¹ Sinusitis is the fifth most common diagnosis for which antibiotics are prescribed in the outpatient setting, with more than $6 billion spent annually in the United States on prescription and over-the-counter medications.^1-3 Can we know with greater certainty when antibiotics are indicated for sinusitis?

A meta-analysis of randomized controlled studies has shown that the likelihood of bacterial sinusitis is increased (sensitivity 76%, specificity 79%) and antibiotics are helpful when a patient exhibits at least 3 of 4 cardinal clinical features: 1) purulent nasal discharge predominating on one side; 2) local facial pain predominating on one side; 3) purulent nasal discharge on both sides; and 4) pus in the nasal cavity.² Although use of these criteria is encouraged, they are based on studies that recruited patients from subspecialty clinics and measured disease-oriented outcomes such as findings on sinus radiographs, CT scans, and sinus puncture with culture.^4-12 Most cases of sinusitis, however, are treated in primary care settings where measuring such outcomes is impractical.

Given the lack of epidemiologic evidence as to which patients would benefit from treatment of sinusitis, primary care physicians face the dilemma of deciding during office encounters which patients should receive antibiotics and which have a viral infection for which symptomatic treatment is indicated.¹³

Our goal was to study the type of patient for whom this dilemma arises and to use clinical improvement as our primary outcome. We randomly assigned patients presenting with sinusitis complaints to receive amoxicillin or placebo, and compared the rates of improvement, time to improvement, and patient’s self-rating of sickness at the end of 2 weeks. We also tested the clinical prediction rule to see if participants with 3 or 4 signs and symptoms had different clinical outcomes than the others.

Methods

Setting

We conducted a randomized double-blind clinical trial of amoxicillin vs placebo. All patients were recruited from a suburban primary care office. Two physicians and one nurse practitioner enrolled and treated all patients over an 18-month period (Oct 1, 2001 to March 31, 2003). The clinicians involved in the study were trained to identify purulent discharge in the nasal cavity. Institutional Review Board approval was obtained from Georgetown University prior to the study. Written informed consent was obtained from all participating patients.

Patients

Patients were eligible to participate if they were 18 years or older; had at least 1 cardinal feature described by the clinical prediction rule: 1) purulent nasal discharge predominating on one side, 2) local facial pain predominating on one side, 3) purulent nasal discharge on both sides, or 4) pus in the nasal cavity; and had symptoms for at least 7 days. Patients were excluded if their histories included antibiotic treatment within the past month, allergy to penicillin, sinus surgery, compromised immunity, pneumonia, or streptococcal pharyngitis.

Randomization

Permuted block randomization stratified for the 3 participating clinicians was used to determine treatment assignment. Patients were given an envelope containing 40 capsules, either a placebo medicine taken twice daily for 10 days or 1000 mg of amoxicillin (500 mg pills) taken twice daily for 10 days. The envelopes were opaque, and each had 40 identical-appearing pills (to ensure allocation concealment). The participating clinicians were naive to the treatment assignments.

Assessment of outcomes

Trained personnel, masked to treatment assignment, conducted follow-up telephone interviews on days 3, 7, and 14 following patients’ visits for sinusitis, to assess clinical improvement. Twelve follow-up questions were asked.

Sample size

The primary outcome used to determine sample size was dichotomous—either “improved” or “not improved” by the end of 2 weeks. Thus, patients were asked, “what day were you entirely improved.” The sample sizes obtained per group (67 for amoxicillin and 68 for placebo) provided 80% power for detecting a change of 25% in rates of improvement.

Statistical analysis

Basic descriptive statistics were used to describe the groups. Baseline characteristics were compared between the 2 groups using chi-square test and Fisher’s exact test for categorical variables. For continuous variables, the Student’s t-test was used; the Wilcoxon Rank Sum test was used for ordinal or skewed variables. Similar statistical tests were used to compare baseline characteristics between the providers and also at the conclusion of the study between the responders for each group.

For the outcome variables, we hypothesized no difference between the groups either in the rates of improvement, times to improvement, or in patients’ self-rating of sickness. The actual proportions improving between the 2 groups were compared using the chi-square test. Relative risk estimates and 95% confidence intervals were calculated to provide measures of risk and precision. Multiple logistic regression was used to compare the rates of improvement adjusting for the number of signs or symptoms classified as either 1, 2, or 3–4, obtained from the clinical prediction rule (Table 1).

The Kaplan-Meier method was used to construct the curves showing the time until patient improvement for each treatment group. The Wilcoxon test was then used to test the statistical significance in these curves (Figure). Cox’s Proportional Hazards regression was used to test for differences in the time to improvement between the groups adjusting for the number of signs or symptoms.

Additionally, a univariate repeated measures analysis of variance model was constructed to compare the 10-point Likert scale scores for the question, “How sick do you feel today?” In this model, the number of signs and symptoms was entered as a covariate in the analysis. Orthogonal contrasts were used as post-hoc tests to compare the difference between the groups within each time point (Table 2 ).

For the subgroup of patients who improved, analysis of covariance was used to compare the mean number of days to improvement between the groups. In this case the number of signs and symptoms was used as the covariate (Table 3). The Kaplan-Meier method and the Wilcoxon test were used to compare the cumulative rates of improvement (Figure). Unadjusted P-values are reported.

Primary analyses were performed using the intention-to-treat principle. All statistical analyses were performed using JMP Software (Product of SAS Institute Inc, Cary, NC). Statistical significance was set at 0.05 and exact P-values are reported.

TABLE 1
Baseline characteristics for amoxicillin and placebo groups

Figure
Kaplan-Meier curve for improvement—amoxicillin (n=67) vs placebo (n=68)*

TABLE 2
Comparison of mean Likert scores by group across follow-up time points Question asked at each time point:

TABLE 3
Mean number of days to improvement by group and number of signs and symptoms (at baseline) for patients who improved

Results

During the 18-month enrollment period, the 3 providers recorded all patients aged >18 years who had at least 1 cardinal feature described by the clinical prediction rule and had symptoms for a minimum of 7 days. Thus, initially 308 patients were approached for enrollment; 173 patients did not qualify after the exclusion criteria were applied, leaving 135 patients for randomization. Sixty-seven received amoxicillin and 68 received placebo. For 11 patients in the amoxicillin arm and 8 in the placebo arm, only baseline data were collected. These patients were then considered as lost to follow-up and were counted as “not improved” in the intention-to-treat analysis.

There were no significant differences (P >.05) in baseline characteristics of the treatment groups (Table 1). Additionally, there were no significant differences in the baseline characteristics between the providers (data not shown).

In the amoxicillin group 32 (48%) had completely improved compared with 25 (37%) in the placebo group (P=.26) after 2 weeks (relative risk of treatment failure=1.3; 95% CI, 0.87–1.94). However, individuals in the amoxicillin group did improve significantly earlier, as the Kaplan-Meier curve demonstrates (Figure). The first person in the amoxicillin group improved on day 3, compared with day 7 in the placebo group. This earlier improvement continued throughout the study (P=.039).

Subgroup analysis of the 57 who demonstrated complete recovery shows the amoxicillin group improved earlier as does the Kaplan-Meier curves in the Figure. In the amoxicillin group, the median day to any improvement was day 8 compared with day 12 for the placebo group (P=.005), while the mean day to improvement for the amoxicillin group was 8.1 days vs 10.7 days for placebo group.

When patients were asked “How sick do you feel today,” the average Likert scores decreased from 6. 1 (day 0) to 2.3 (day 14), and 6.3 (day 0) to 2.8 (day 14), in the amoxicillin and placebo groups, respectively. At each time point, there were no significant clinical or statistical differences between the 2 groups in how they rated their improvement (Table 2). Furthermore, examining only those who reported total improvement within 14 days showed no differences among groups.

No statistically significant differences were observed between the treatment groups that entailed the clinical prediction rule. However, in the patients who were improved at 14 days, the average number of days to improvement was consistently between 2 to 2.5 days shorter in the amoxicillin group compared with placebo (Table 3).

Side effects

No patients dropped out of the study due to adverse side effects (Table 4). There were no serious or unexpected side effects, with the majority related to gastrointestinal problems, such as diarrhea and abdominal pain.

TABLE 4
A Frequency of reported side effects by group

Discussion

With respect to the patient-oriented outcome of clinical improvement, amoxicillin provided no significant benefit over placebo in the treatment of patients presenting with sinusitis complaints. On average our patients who had symptoms for 11 days prior to enrollment and are typical of patients that are often recommended for treatment with antibiotics.^14,15

Our findings are consistent with others in which the overall benefit of antibiotics was minimal or nonexistent.^16,18 But among individuals who did improve, those who received amoxicillin improved much earlier, both clinically and statistically. Unfortunately we were not able to specify those who are likely to improve. Clearly, further patient-oriented outcome studies are needed to help primary care physicians decide which patients may benefit from antibiotic treatment.

Antibiotics have not been shown to prevent the sequelae of acute sinusitis. One of the major difficulties in treating sinusitis is the lack of agreement about which outcomes are desired.^19,20 Nearly 66% of patients diagnosed with sinusitis will get better without treatment, though nearly two thirds of patients will continue to have such symptoms as cough and nasal discharge for up to 3 weeks.^21,22 Thus, we believe that to give antibiotics only to individuals who would truly benefit from them, policy makers, primary care physicians, and patients need to reassess clinically what constitutes sinusitis, and what outcomes are most desired. If the goal is to cure purulent nasal discharge, we are likely over-treating with antibiotics; as our study showed, after 2 weeks most patients in both groups still had nasal symptoms.

Our pilot of the clinical prediction rule failed to predict a proper response to antibiotics or the time to improvement. Although our numbers were not large, no trend was observed towards improvement in individuals with a higher score on the clinical prediction rule.

Our study has some important limitations. Interestingly we found different results when we used the dichotomous outcome of totally improved versus the 10-point Likert scale. A priori we decided our primary outcome was the dichotomous improvement, but which measure is more important and should be used is open to varying interpretations. Additionally, our study office unexpectedly closed and thus we could not recruit the number of patients we initially had planned. This limited our power to find differences between groups based on the number of cardinal clinical features. We encountered noncompliance with follow-up, as expected with the study design. We also arbitrarily stopped follow-up at 14 days, and cases that had not entirely improved were considered clinical failures in all but the Likert scale analysis. It is possible our results may have differed if we had continued to follow patients at 21 or 28 days, or if we had conducted the study at more than one office.

Methodologically, we conducted a rigorous study and showed that patients diagnosed with clinical sinusitis fared no better with amoxicillin or placebo, when measuring the patient-oriented outcome of complete improvement. But a subgroup of patients who were given antibiotics did improve at a much quicker rate. The difficulty is in clinically identifying this group and treating them with antibiotics. Conversely, using antibiotics in patients unnecessarily would only cause potential individual and societal harm. More clinically oriented studies need to be conducted to address this issue and elucidate what signs and symptoms these patients exhibit, to help clarify who should be treated with antibiotics.

ACKNOWLEDGMENTS

When this article was prepared, Dan Merenstein was an assistant professor of Family Medicine and Pediatrics at Georgetown University. This study was part of the Capricorn Research Network of Georgetown University. This projectwas supported by a grant from the American Academy ofFamily Physicians and the American Academy of FamilyPhysicians Foundation “Joint AAFP/F-AAFP Grant AwardsProgram” (JGAP). Support was also provided by the CapitolArea Primary Care Research Network. Research presentedat NAPRCG 2003, Banff, Canada.

We thank Joel Merenstein for insightful feedback and intelligent comments about study design and input with manuscript. We thank Goutham Rao and Traci Reisner for editorial help. We thank Community Drug Compounding Center of Pittsburgh and pharmacist Susan Freedenberg for drug development.

Corresponding author
Dan Merenstein, MD, Robert Wood Johnson Clinical Scholar, The Johns Hopkins Hospital, 600 North Wolfe St., Carnegie 291, Baltimore, MD 21287-6220. E-mail: dmerenstein@jhu.edu.

It is estimated that adults have 2 to 3 colds a year, of which just 0.5% to 2% are complicated by bacterial sinusitis. However, primary care physicians treat over half of these colds with antibiotics.¹ Sinusitis is the fifth most common diagnosis for which antibiotics are prescribed in the outpatient setting, with more than $6 billion spent annually in the United States on prescription and over-the-counter medications.^1-3 Can we know with greater certainty when antibiotics are indicated for sinusitis?

A meta-analysis of randomized controlled studies has shown that the likelihood of bacterial sinusitis is increased (sensitivity 76%, specificity 79%) and antibiotics are helpful when a patient exhibits at least 3 of 4 cardinal clinical features: 1) purulent nasal discharge predominating on one side; 2) local facial pain predominating on one side; 3) purulent nasal discharge on both sides; and 4) pus in the nasal cavity.² Although use of these criteria is encouraged, they are based on studies that recruited patients from subspecialty clinics and measured disease-oriented outcomes such as findings on sinus radiographs, CT scans, and sinus puncture with culture.^4-12 Most cases of sinusitis, however, are treated in primary care settings where measuring such outcomes is impractical.

Given the lack of epidemiologic evidence as to which patients would benefit from treatment of sinusitis, primary care physicians face the dilemma of deciding during office encounters which patients should receive antibiotics and which have a viral infection for which symptomatic treatment is indicated.¹³

Our goal was to study the type of patient for whom this dilemma arises and to use clinical improvement as our primary outcome. We randomly assigned patients presenting with sinusitis complaints to receive amoxicillin or placebo, and compared the rates of improvement, time to improvement, and patient’s self-rating of sickness at the end of 2 weeks. We also tested the clinical prediction rule to see if participants with 3 or 4 signs and symptoms had different clinical outcomes than the others.

Methods

Setting

We conducted a randomized double-blind clinical trial of amoxicillin vs placebo. All patients were recruited from a suburban primary care office. Two physicians and one nurse practitioner enrolled and treated all patients over an 18-month period (Oct 1, 2001 to March 31, 2003). The clinicians involved in the study were trained to identify purulent discharge in the nasal cavity. Institutional Review Board approval was obtained from Georgetown University prior to the study. Written informed consent was obtained from all participating patients.

Patients

Patients were eligible to participate if they were 18 years or older; had at least 1 cardinal feature described by the clinical prediction rule: 1) purulent nasal discharge predominating on one side, 2) local facial pain predominating on one side, 3) purulent nasal discharge on both sides, or 4) pus in the nasal cavity; and had symptoms for at least 7 days. Patients were excluded if their histories included antibiotic treatment within the past month, allergy to penicillin, sinus surgery, compromised immunity, pneumonia, or streptococcal pharyngitis.

Randomization

Permuted block randomization stratified for the 3 participating clinicians was used to determine treatment assignment. Patients were given an envelope containing 40 capsules, either a placebo medicine taken twice daily for 10 days or 1000 mg of amoxicillin (500 mg pills) taken twice daily for 10 days. The envelopes were opaque, and each had 40 identical-appearing pills (to ensure allocation concealment). The participating clinicians were naive to the treatment assignments.

Assessment of outcomes

Trained personnel, masked to treatment assignment, conducted follow-up telephone interviews on days 3, 7, and 14 following patients’ visits for sinusitis, to assess clinical improvement. Twelve follow-up questions were asked.

Sample size

The primary outcome used to determine sample size was dichotomous—either “improved” or “not improved” by the end of 2 weeks. Thus, patients were asked, “what day were you entirely improved.” The sample sizes obtained per group (67 for amoxicillin and 68 for placebo) provided 80% power for detecting a change of 25% in rates of improvement.

Statistical analysis

Basic descriptive statistics were used to describe the groups. Baseline characteristics were compared between the 2 groups using chi-square test and Fisher’s exact test for categorical variables. For continuous variables, the Student’s t-test was used; the Wilcoxon Rank Sum test was used for ordinal or skewed variables. Similar statistical tests were used to compare baseline characteristics between the providers and also at the conclusion of the study between the responders for each group.

For the outcome variables, we hypothesized no difference between the groups either in the rates of improvement, times to improvement, or in patients’ self-rating of sickness. The actual proportions improving between the 2 groups were compared using the chi-square test. Relative risk estimates and 95% confidence intervals were calculated to provide measures of risk and precision. Multiple logistic regression was used to compare the rates of improvement adjusting for the number of signs or symptoms classified as either 1, 2, or 3–4, obtained from the clinical prediction rule (Table 1).

The Kaplan-Meier method was used to construct the curves showing the time until patient improvement for each treatment group. The Wilcoxon test was then used to test the statistical significance in these curves (Figure). Cox’s Proportional Hazards regression was used to test for differences in the time to improvement between the groups adjusting for the number of signs or symptoms.

Additionally, a univariate repeated measures analysis of variance model was constructed to compare the 10-point Likert scale scores for the question, “How sick do you feel today?” In this model, the number of signs and symptoms was entered as a covariate in the analysis. Orthogonal contrasts were used as post-hoc tests to compare the difference between the groups within each time point (Table 2 ).

For the subgroup of patients who improved, analysis of covariance was used to compare the mean number of days to improvement between the groups. In this case the number of signs and symptoms was used as the covariate (Table 3). The Kaplan-Meier method and the Wilcoxon test were used to compare the cumulative rates of improvement (Figure). Unadjusted P-values are reported.

Primary analyses were performed using the intention-to-treat principle. All statistical analyses were performed using JMP Software (Product of SAS Institute Inc, Cary, NC). Statistical significance was set at 0.05 and exact P-values are reported.

TABLE 1
Baseline characteristics for amoxicillin and placebo groups

Figure
Kaplan-Meier curve for improvement—amoxicillin (n=67) vs placebo (n=68)*

TABLE 2
Comparison of mean Likert scores by group across follow-up time points Question asked at each time point:

TABLE 3
Mean number of days to improvement by group and number of signs and symptoms (at baseline) for patients who improved

Results

During the 18-month enrollment period, the 3 providers recorded all patients aged >18 years who had at least 1 cardinal feature described by the clinical prediction rule and had symptoms for a minimum of 7 days. Thus, initially 308 patients were approached for enrollment; 173 patients did not qualify after the exclusion criteria were applied, leaving 135 patients for randomization. Sixty-seven received amoxicillin and 68 received placebo. For 11 patients in the amoxicillin arm and 8 in the placebo arm, only baseline data were collected. These patients were then considered as lost to follow-up and were counted as “not improved” in the intention-to-treat analysis.

There were no significant differences (P >.05) in baseline characteristics of the treatment groups (Table 1). Additionally, there were no significant differences in the baseline characteristics between the providers (data not shown).

In the amoxicillin group 32 (48%) had completely improved compared with 25 (37%) in the placebo group (P=.26) after 2 weeks (relative risk of treatment failure=1.3; 95% CI, 0.87–1.94). However, individuals in the amoxicillin group did improve significantly earlier, as the Kaplan-Meier curve demonstrates (Figure). The first person in the amoxicillin group improved on day 3, compared with day 7 in the placebo group. This earlier improvement continued throughout the study (P=.039).

Subgroup analysis of the 57 who demonstrated complete recovery shows the amoxicillin group improved earlier as does the Kaplan-Meier curves in the Figure. In the amoxicillin group, the median day to any improvement was day 8 compared with day 12 for the placebo group (P=.005), while the mean day to improvement for the amoxicillin group was 8.1 days vs 10.7 days for placebo group.

When patients were asked “How sick do you feel today,” the average Likert scores decreased from 6. 1 (day 0) to 2.3 (day 14), and 6.3 (day 0) to 2.8 (day 14), in the amoxicillin and placebo groups, respectively. At each time point, there were no significant clinical or statistical differences between the 2 groups in how they rated their improvement (Table 2). Furthermore, examining only those who reported total improvement within 14 days showed no differences among groups.

No statistically significant differences were observed between the treatment groups that entailed the clinical prediction rule. However, in the patients who were improved at 14 days, the average number of days to improvement was consistently between 2 to 2.5 days shorter in the amoxicillin group compared with placebo (Table 3).

Side effects

No patients dropped out of the study due to adverse side effects (Table 4). There were no serious or unexpected side effects, with the majority related to gastrointestinal problems, such as diarrhea and abdominal pain.

TABLE 4
A Frequency of reported side effects by group

Discussion

With respect to the patient-oriented outcome of clinical improvement, amoxicillin provided no significant benefit over placebo in the treatment of patients presenting with sinusitis complaints. On average our patients who had symptoms for 11 days prior to enrollment and are typical of patients that are often recommended for treatment with antibiotics.^14,15

Our findings are consistent with others in which the overall benefit of antibiotics was minimal or nonexistent.^16,18 But among individuals who did improve, those who received amoxicillin improved much earlier, both clinically and statistically. Unfortunately we were not able to specify those who are likely to improve. Clearly, further patient-oriented outcome studies are needed to help primary care physicians decide which patients may benefit from antibiotic treatment.

Antibiotics have not been shown to prevent the sequelae of acute sinusitis. One of the major difficulties in treating sinusitis is the lack of agreement about which outcomes are desired.^19,20 Nearly 66% of patients diagnosed with sinusitis will get better without treatment, though nearly two thirds of patients will continue to have such symptoms as cough and nasal discharge for up to 3 weeks.^21,22 Thus, we believe that to give antibiotics only to individuals who would truly benefit from them, policy makers, primary care physicians, and patients need to reassess clinically what constitutes sinusitis, and what outcomes are most desired. If the goal is to cure purulent nasal discharge, we are likely over-treating with antibiotics; as our study showed, after 2 weeks most patients in both groups still had nasal symptoms.

Our pilot of the clinical prediction rule failed to predict a proper response to antibiotics or the time to improvement. Although our numbers were not large, no trend was observed towards improvement in individuals with a higher score on the clinical prediction rule.

Our study has some important limitations. Interestingly we found different results when we used the dichotomous outcome of totally improved versus the 10-point Likert scale. A priori we decided our primary outcome was the dichotomous improvement, but which measure is more important and should be used is open to varying interpretations. Additionally, our study office unexpectedly closed and thus we could not recruit the number of patients we initially had planned. This limited our power to find differences between groups based on the number of cardinal clinical features. We encountered noncompliance with follow-up, as expected with the study design. We also arbitrarily stopped follow-up at 14 days, and cases that had not entirely improved were considered clinical failures in all but the Likert scale analysis. It is possible our results may have differed if we had continued to follow patients at 21 or 28 days, or if we had conducted the study at more than one office.

Methodologically, we conducted a rigorous study and showed that patients diagnosed with clinical sinusitis fared no better with amoxicillin or placebo, when measuring the patient-oriented outcome of complete improvement. But a subgroup of patients who were given antibiotics did improve at a much quicker rate. The difficulty is in clinically identifying this group and treating them with antibiotics. Conversely, using antibiotics in patients unnecessarily would only cause potential individual and societal harm. More clinically oriented studies need to be conducted to address this issue and elucidate what signs and symptoms these patients exhibit, to help clarify who should be treated with antibiotics.

ACKNOWLEDGMENTS

When this article was prepared, Dan Merenstein was an assistant professor of Family Medicine and Pediatrics at Georgetown University. This study was part of the Capricorn Research Network of Georgetown University. This projectwas supported by a grant from the American Academy ofFamily Physicians and the American Academy of FamilyPhysicians Foundation “Joint AAFP/F-AAFP Grant AwardsProgram” (JGAP). Support was also provided by the CapitolArea Primary Care Research Network. Research presentedat NAPRCG 2003, Banff, Canada.

We thank Joel Merenstein for insightful feedback and intelligent comments about study design and input with manuscript. We thank Goutham Rao and Traci Reisner for editorial help. We thank Community Drug Compounding Center of Pittsburgh and pharmacist Susan Freedenberg for drug development.

Corresponding author
Dan Merenstein, MD, Robert Wood Johnson Clinical Scholar, The Johns Hopkins Hospital, 600 North Wolfe St., Carnegie 291, Baltimore, MD 21287-6220. E-mail: dmerenstein@jhu.edu.

• BACKGROUND: Acute anal fissures generally heal spontaneously with minimal or no intervention. Conversely, chronic anal fissures are traditionally treated with surgery. Therapies such as botulinum toxin, isosorbide dinitrate, and glyceryl tinitrate have shown some benefit, but their side-effect profiles are substantial. With the knowledge that topical nifedipine has been shown to relax smooth muscle, lower anal resting pressure, relieve pain, and heal acute anal fissures, these authors studied its effect on chronic anal fissures.
• POPULATION STUDIED: Patients were recruited from the emergency surgery and gastroenterology center in Italy that conducted the study. Inclusion criteria were chronic anal fissure and age older than 18 years. Chronic anal fissure was assessed by clinical examination and a history of anal pain on defecation for longer than 2 months that did not resolve with stool softeners and simple anesthetic agents. Exclusion criteria were pregnancy, allergy to nifedipine or lidocaine, and complications warranting surgery.
• STUDY DESIGN AND VALIDITY: This was a prospective, randomized, double-blind study. The control group received 1.5% lidocaine and 1% hydrocortisone acetate, and the treatment group received 1.5% lidocaine and 0.3% nifedipine. The ointments were applied every 12 hours for 6 weeks. The ointments were indistinguishable, and all parties were blinded with proper allocation concealment. Data analysis was by intention-to-treat. The groups were randomly assigned and had similar baseline characteristics.
• OUTCOMES MEASURED: Healing of the chronic anal fissure was the primary outcome and was defined by anoscopy when epithelialization or formation of a scar was achieved at 42 days. Patients also subjectively rated pain as absent, modest, or persistent at day 21. Manometric studies were used as a secondary measure of clinical improvement and were measured at baseline and 21 days.
• RESULTS: Of the 55 patients in the nifedipine group, 94.5% healed clinically at 42 days and 87.3% reported no pain at 21 days. Conversely, of the 55 patients in the control group evaluated at the same intervals, 16.4% healed and 10.9% reported no pain (P<.001; number needed to treat=1.3).

• BACKGROUND: Acute anal fissures generally heal spontaneously with minimal or no intervention. Conversely, chronic anal fissures are traditionally treated with surgery. Therapies such as botulinum toxin, isosorbide dinitrate, and glyceryl tinitrate have shown some benefit, but their side-effect profiles are substantial. With the knowledge that topical nifedipine has been shown to relax smooth muscle, lower anal resting pressure, relieve pain, and heal acute anal fissures, these authors studied its effect on chronic anal fissures.
• POPULATION STUDIED: Patients were recruited from the emergency surgery and gastroenterology center in Italy that conducted the study. Inclusion criteria were chronic anal fissure and age older than 18 years. Chronic anal fissure was assessed by clinical examination and a history of anal pain on defecation for longer than 2 months that did not resolve with stool softeners and simple anesthetic agents. Exclusion criteria were pregnancy, allergy to nifedipine or lidocaine, and complications warranting surgery.
• STUDY DESIGN AND VALIDITY: This was a prospective, randomized, double-blind study. The control group received 1.5% lidocaine and 1% hydrocortisone acetate, and the treatment group received 1.5% lidocaine and 0.3% nifedipine. The ointments were applied every 12 hours for 6 weeks. The ointments were indistinguishable, and all parties were blinded with proper allocation concealment. Data analysis was by intention-to-treat. The groups were randomly assigned and had similar baseline characteristics.
• OUTCOMES MEASURED: Healing of the chronic anal fissure was the primary outcome and was defined by anoscopy when epithelialization or formation of a scar was achieved at 42 days. Patients also subjectively rated pain as absent, modest, or persistent at day 21. Manometric studies were used as a secondary measure of clinical improvement and were measured at baseline and 21 days.
• RESULTS: Of the 55 patients in the nifedipine group, 94.5% healed clinically at 42 days and 87.3% reported no pain at 21 days. Conversely, of the 55 patients in the control group evaluated at the same intervals, 16.4% healed and 10.9% reported no pain (P<.001; number needed to treat=1.3).

• BACKGROUND: Acute anal fissures generally heal spontaneously with minimal or no intervention. Conversely, chronic anal fissures are traditionally treated with surgery. Therapies such as botulinum toxin, isosorbide dinitrate, and glyceryl tinitrate have shown some benefit, but their side-effect profiles are substantial. With the knowledge that topical nifedipine has been shown to relax smooth muscle, lower anal resting pressure, relieve pain, and heal acute anal fissures, these authors studied its effect on chronic anal fissures.
• POPULATION STUDIED: Patients were recruited from the emergency surgery and gastroenterology center in Italy that conducted the study. Inclusion criteria were chronic anal fissure and age older than 18 years. Chronic anal fissure was assessed by clinical examination and a history of anal pain on defecation for longer than 2 months that did not resolve with stool softeners and simple anesthetic agents. Exclusion criteria were pregnancy, allergy to nifedipine or lidocaine, and complications warranting surgery.
• STUDY DESIGN AND VALIDITY: This was a prospective, randomized, double-blind study. The control group received 1.5% lidocaine and 1% hydrocortisone acetate, and the treatment group received 1.5% lidocaine and 0.3% nifedipine. The ointments were applied every 12 hours for 6 weeks. The ointments were indistinguishable, and all parties were blinded with proper allocation concealment. Data analysis was by intention-to-treat. The groups were randomly assigned and had similar baseline characteristics.
• OUTCOMES MEASURED: Healing of the chronic anal fissure was the primary outcome and was defined by anoscopy when epithelialization or formation of a scar was achieved at 42 days. Patients also subjectively rated pain as absent, modest, or persistent at day 21. Manometric studies were used as a secondary measure of clinical improvement and were measured at baseline and 21 days.
• RESULTS: Of the 55 patients in the nifedipine group, 94.5% healed clinically at 42 days and 87.3% reported no pain at 21 days. Conversely, of the 55 patients in the control group evaluated at the same intervals, 16.4% healed and 10.9% reported no pain (P<.001; number needed to treat=1.3).

BACKGROUND: Significant morbidity can occur in untreated patients with Lyme disease. Currently the Infectious Disease Society of America (IDSA) recommends treatment only in the presence of erythema migrans or seropositivity with symptoms of systemic disease. Although the IDSA does not recommend antimicrobial prophylaxis to patients with a documented tick bite, it may be possible to prevent Lyme disease by treating patients prophylactically after removing the tick Ixodes scapularis.

POPULATION STUDIED: Study subjects were recruited from Westchester County, New York, an area in which Lyme disease is hyperendemic. Inclusion criteria included age older than 12 years with a history of having removed an Ixodes scapularis tick within 72 hours of enrollment. Subjects whose ticks were later shown to not be Ixodes scapularis were included only in the analysis of safety. Other exclusion criteria included having been vaccinated against Lyme disease, having a rash consistent with erythema migrans, actively taking or having recently completed a course of antibiotics effective against Borrelia burgdorferi, being pregnant or lactating, and not having the tick available for analysis.

STUDY DESIGN AND VALIDITY: The study was a randomized controlled double-blind trial of 506 patients with a documented bite from the Ixodes scapularis tick. The subjects received either a single dose of 200 mg of doxycycline or matched placebo. Ticks were examined by a medical entomologist who confirmed the species type and the life cycle stage as either adult or nymphal. Ticks were also classified as unfed (flat) or partly fed (engorged) on the basis of visual inspection. Observers blind to treatment group assignment evaluated patients at enrollment, 3 weeks, and 6 weeks. Medications were swallowed by direct observation to ensure 100% compliance. The follow-up completion rate of all 3 visits was 89%.

OUTCOMES MEASURED: The primary outcome was the development of erythema migrans at the site of the tick bite. Secondary outcomes were erythema migrans at secondary sites and laboratory evidence of Borrelia burgdorferi.

RESULTS: In the doxycycline group, 1 of 235 subjects developed erythema migrans, compared with 8 of 247 in the placebo group (0.4% vs 3.2%, P <.04; number needed to treat = 36). Serologic confirmation of Lyme disease occurred in 8 of the 9 patients with erythema migrans. Objective systemic manifestations of Lyme disease and asymptomatic seroconversions were not observed in any patient. Adverse events were more common in the treatment group (30% vs 11%, P <.001) and were primarily gastrointestinal. A subgroup analysis demonstrated that none of the 116 patients in the placebo group that had unfed (flat) ticks developed erythema migrans. Ticks removed within 72 hours were also very unlikely to transmit disease.

BACKGROUND: Significant morbidity can occur in untreated patients with Lyme disease. Currently the Infectious Disease Society of America (IDSA) recommends treatment only in the presence of erythema migrans or seropositivity with symptoms of systemic disease. Although the IDSA does not recommend antimicrobial prophylaxis to patients with a documented tick bite, it may be possible to prevent Lyme disease by treating patients prophylactically after removing the tick Ixodes scapularis.

POPULATION STUDIED: Study subjects were recruited from Westchester County, New York, an area in which Lyme disease is hyperendemic. Inclusion criteria included age older than 12 years with a history of having removed an Ixodes scapularis tick within 72 hours of enrollment. Subjects whose ticks were later shown to not be Ixodes scapularis were included only in the analysis of safety. Other exclusion criteria included having been vaccinated against Lyme disease, having a rash consistent with erythema migrans, actively taking or having recently completed a course of antibiotics effective against Borrelia burgdorferi, being pregnant or lactating, and not having the tick available for analysis.

STUDY DESIGN AND VALIDITY: The study was a randomized controlled double-blind trial of 506 patients with a documented bite from the Ixodes scapularis tick. The subjects received either a single dose of 200 mg of doxycycline or matched placebo. Ticks were examined by a medical entomologist who confirmed the species type and the life cycle stage as either adult or nymphal. Ticks were also classified as unfed (flat) or partly fed (engorged) on the basis of visual inspection. Observers blind to treatment group assignment evaluated patients at enrollment, 3 weeks, and 6 weeks. Medications were swallowed by direct observation to ensure 100% compliance. The follow-up completion rate of all 3 visits was 89%.

OUTCOMES MEASURED: The primary outcome was the development of erythema migrans at the site of the tick bite. Secondary outcomes were erythema migrans at secondary sites and laboratory evidence of Borrelia burgdorferi.

RESULTS: In the doxycycline group, 1 of 235 subjects developed erythema migrans, compared with 8 of 247 in the placebo group (0.4% vs 3.2%, P <.04; number needed to treat = 36). Serologic confirmation of Lyme disease occurred in 8 of the 9 patients with erythema migrans. Objective systemic manifestations of Lyme disease and asymptomatic seroconversions were not observed in any patient. Adverse events were more common in the treatment group (30% vs 11%, P <.001) and were primarily gastrointestinal. A subgroup analysis demonstrated that none of the 116 patients in the placebo group that had unfed (flat) ticks developed erythema migrans. Ticks removed within 72 hours were also very unlikely to transmit disease.

BACKGROUND: Significant morbidity can occur in untreated patients with Lyme disease. Currently the Infectious Disease Society of America (IDSA) recommends treatment only in the presence of erythema migrans or seropositivity with symptoms of systemic disease. Although the IDSA does not recommend antimicrobial prophylaxis to patients with a documented tick bite, it may be possible to prevent Lyme disease by treating patients prophylactically after removing the tick Ixodes scapularis.

POPULATION STUDIED: Study subjects were recruited from Westchester County, New York, an area in which Lyme disease is hyperendemic. Inclusion criteria included age older than 12 years with a history of having removed an Ixodes scapularis tick within 72 hours of enrollment. Subjects whose ticks were later shown to not be Ixodes scapularis were included only in the analysis of safety. Other exclusion criteria included having been vaccinated against Lyme disease, having a rash consistent with erythema migrans, actively taking or having recently completed a course of antibiotics effective against Borrelia burgdorferi, being pregnant or lactating, and not having the tick available for analysis.

STUDY DESIGN AND VALIDITY: The study was a randomized controlled double-blind trial of 506 patients with a documented bite from the Ixodes scapularis tick. The subjects received either a single dose of 200 mg of doxycycline or matched placebo. Ticks were examined by a medical entomologist who confirmed the species type and the life cycle stage as either adult or nymphal. Ticks were also classified as unfed (flat) or partly fed (engorged) on the basis of visual inspection. Observers blind to treatment group assignment evaluated patients at enrollment, 3 weeks, and 6 weeks. Medications were swallowed by direct observation to ensure 100% compliance. The follow-up completion rate of all 3 visits was 89%.

OUTCOMES MEASURED: The primary outcome was the development of erythema migrans at the site of the tick bite. Secondary outcomes were erythema migrans at secondary sites and laboratory evidence of Borrelia burgdorferi.

RESULTS: In the doxycycline group, 1 of 235 subjects developed erythema migrans, compared with 8 of 247 in the placebo group (0.4% vs 3.2%, P <.04; number needed to treat = 36). Serologic confirmation of Lyme disease occurred in 8 of the 9 patients with erythema migrans. Objective systemic manifestations of Lyme disease and asymptomatic seroconversions were not observed in any patient. Adverse events were more common in the treatment group (30% vs 11%, P <.001) and were primarily gastrointestinal. A subgroup analysis demonstrated that none of the 116 patients in the placebo group that had unfed (flat) ticks developed erythema migrans. Ticks removed within 72 hours were also very unlikely to transmit disease.

BACKGROUND: No pharmacologic intervention has been demonstrated to affect health deterioration or disease advancement of COPD. Use of inhaled steroids in moderate doses is common, but a controlled trial has shown that such treatment results in only a small benefit in changes in forced expiratory volume in 1 second (FEV1) and minimal improvement in clinical parameters.¹

POPULATION STUDIED: Patients were current or former smokers aged between 40 and 75 years. All had nonasthmatic COPD defined as an FEV1 less than 85% of predicted, and an FEV1/forced vital capacity percentage less than 70% with less than 10% improvement from inhaled b-agonists. Previous use of inhaled or oral corticosteriods was permitted. Patients were excluded if they had a life expectancy of less than 5 years from concurrent diseases or if they used b-blockers. Concurrent use of theophyllines and bronchodilators was allowed during the study.

STUDY DESIGN AND VALIDITY: This was a randomized placebo-controlled double-blinded study of 751 patients. There was no mention of allocation concealment. After an 8-week period of withdrawal from steroid use, patients received 14 days of oral prednisolone to determine whether a response to acute corticosteroids could predict a response to long-term inhaled corticosteroids. Patients then received either placebo or 500 mg fluticasone using a metered dose inhaler with a spacer twice daily. Patients were evaluated every 3 months for 3 years. Health status was measured by the St. George’s respiratory questionnaire; a 4-point change in this 100-point scale was judged to be clinically significant. An exacerbation was defined as worsening of respiratory symptoms requiring treatment with oral cortico- steroids or antibiotics.

OUTCOMES MEASURED: The primary end point was the annual decline in FEV1. Secondary end points were the frequencies of exacerbations, changes in health status, withdrawals because of respiratory disease, morning serum cortisol concentrations, and adverse events.

RESULTS: There was no difference in the decline of respiratory function as measured by FEV1 over the 3 years of the study in the fluticasone or placebo groups (59 mL/year vs 50 mL/year). The yearly exacerbation rate was lower in the fluticasone group than in the placebo group (0.99 vs 1.32 per year; P=.026). This resulted in 3 patients treated with high-dose fluticasone for a year (at a retail pharmacy cost in the United States of $1500 per patient) to prevent 1 exacerbation requiring steroids or antibiotics (number needed to treat=3). Health status measured by the increase in questionnaire score declined at a slower rate in the fluticasone group than in the placebo group (2.0 vs 3.2 units/year; P=.004). Although this was statistically significant, the difference is unlikely to be clinically relevant. Adverse effects were similar in each group. The response to oral prednisolone did not predict a subsequent response to inhaled corticosteroids.

BACKGROUND: No pharmacologic intervention has been demonstrated to affect health deterioration or disease advancement of COPD. Use of inhaled steroids in moderate doses is common, but a controlled trial has shown that such treatment results in only a small benefit in changes in forced expiratory volume in 1 second (FEV1) and minimal improvement in clinical parameters.¹

POPULATION STUDIED: Patients were current or former smokers aged between 40 and 75 years. All had nonasthmatic COPD defined as an FEV1 less than 85% of predicted, and an FEV1/forced vital capacity percentage less than 70% with less than 10% improvement from inhaled b-agonists. Previous use of inhaled or oral corticosteriods was permitted. Patients were excluded if they had a life expectancy of less than 5 years from concurrent diseases or if they used b-blockers. Concurrent use of theophyllines and bronchodilators was allowed during the study.

STUDY DESIGN AND VALIDITY: This was a randomized placebo-controlled double-blinded study of 751 patients. There was no mention of allocation concealment. After an 8-week period of withdrawal from steroid use, patients received 14 days of oral prednisolone to determine whether a response to acute corticosteroids could predict a response to long-term inhaled corticosteroids. Patients then received either placebo or 500 mg fluticasone using a metered dose inhaler with a spacer twice daily. Patients were evaluated every 3 months for 3 years. Health status was measured by the St. George’s respiratory questionnaire; a 4-point change in this 100-point scale was judged to be clinically significant. An exacerbation was defined as worsening of respiratory symptoms requiring treatment with oral cortico- steroids or antibiotics.

OUTCOMES MEASURED: The primary end point was the annual decline in FEV1. Secondary end points were the frequencies of exacerbations, changes in health status, withdrawals because of respiratory disease, morning serum cortisol concentrations, and adverse events.

RESULTS: There was no difference in the decline of respiratory function as measured by FEV1 over the 3 years of the study in the fluticasone or placebo groups (59 mL/year vs 50 mL/year). The yearly exacerbation rate was lower in the fluticasone group than in the placebo group (0.99 vs 1.32 per year; P=.026). This resulted in 3 patients treated with high-dose fluticasone for a year (at a retail pharmacy cost in the United States of $1500 per patient) to prevent 1 exacerbation requiring steroids or antibiotics (number needed to treat=3). Health status measured by the increase in questionnaire score declined at a slower rate in the fluticasone group than in the placebo group (2.0 vs 3.2 units/year; P=.004). Although this was statistically significant, the difference is unlikely to be clinically relevant. Adverse effects were similar in each group. The response to oral prednisolone did not predict a subsequent response to inhaled corticosteroids.

BACKGROUND: No pharmacologic intervention has been demonstrated to affect health deterioration or disease advancement of COPD. Use of inhaled steroids in moderate doses is common, but a controlled trial has shown that such treatment results in only a small benefit in changes in forced expiratory volume in 1 second (FEV1) and minimal improvement in clinical parameters.¹

POPULATION STUDIED: Patients were current or former smokers aged between 40 and 75 years. All had nonasthmatic COPD defined as an FEV1 less than 85% of predicted, and an FEV1/forced vital capacity percentage less than 70% with less than 10% improvement from inhaled b-agonists. Previous use of inhaled or oral corticosteriods was permitted. Patients were excluded if they had a life expectancy of less than 5 years from concurrent diseases or if they used b-blockers. Concurrent use of theophyllines and bronchodilators was allowed during the study.

STUDY DESIGN AND VALIDITY: This was a randomized placebo-controlled double-blinded study of 751 patients. There was no mention of allocation concealment. After an 8-week period of withdrawal from steroid use, patients received 14 days of oral prednisolone to determine whether a response to acute corticosteroids could predict a response to long-term inhaled corticosteroids. Patients then received either placebo or 500 mg fluticasone using a metered dose inhaler with a spacer twice daily. Patients were evaluated every 3 months for 3 years. Health status was measured by the St. George’s respiratory questionnaire; a 4-point change in this 100-point scale was judged to be clinically significant. An exacerbation was defined as worsening of respiratory symptoms requiring treatment with oral cortico- steroids or antibiotics.

OUTCOMES MEASURED: The primary end point was the annual decline in FEV1. Secondary end points were the frequencies of exacerbations, changes in health status, withdrawals because of respiratory disease, morning serum cortisol concentrations, and adverse events.

RESULTS: There was no difference in the decline of respiratory function as measured by FEV1 over the 3 years of the study in the fluticasone or placebo groups (59 mL/year vs 50 mL/year). The yearly exacerbation rate was lower in the fluticasone group than in the placebo group (0.99 vs 1.32 per year; P=.026). This resulted in 3 patients treated with high-dose fluticasone for a year (at a retail pharmacy cost in the United States of $1500 per patient) to prevent 1 exacerbation requiring steroids or antibiotics (number needed to treat=3). Health status measured by the increase in questionnaire score declined at a slower rate in the fluticasone group than in the placebo group (2.0 vs 3.2 units/year; P=.004). Although this was statistically significant, the difference is unlikely to be clinically relevant. Adverse effects were similar in each group. The response to oral prednisolone did not predict a subsequent response to inhaled corticosteroids.