Barbara J. Rutledge

The meningococcal C conjugate vaccine can be safely and effectively administered to children with juvenile idiopathic arthritis, without aggravating disease activity or increasing relapse frequency, according to study results.

In 2002, Dutch health authorities initiated a national campaign to promote vaccination of all children aged 1–19 years against meningococcal serogroup C disease, but guideline recommendations were nonspecific regarding exclusion of patients with autoimmune diseases and patients on immunosuppressive therapy.

Therefore, Dr. Evelien Zonneveld-Huijssoon, of Wilhelmina Children's Hospital at University Medical Center Utrecht (the Netherlands), and colleagues undertook a study to determine whether vaccination exacerbates disease activity in patients with autoimmune disease and to assess the effect of immunosuppressive medication on vaccine efficacy.

Children with juvenile idiopathic arthritis (JIA) were selected as the study population. Investigators monitored JIA disease activity and immune responses before and after inoculation with a meningococcal C (MenC) conjugate vaccine (Arthritis Rheum. 2007;56:639–46).

A total of 234 JIA patients enrolled in the study. All patients were aged 1–19 years and attended one of the five pediatric rheumatology outpatient clinics participating in the study. The majority of the patients were female (65%), and mean disease duration was 5.9 years.

Patients were followed clinically for 6 months before and after vaccination. The primary outcome measure was disease relapse. Regardless of JIA disease activity, each patient received a single intramuscular dose of the vaccine during the national vaccination campaign and reported the vaccination date on a study questionnaire. Patients provided blood samples for serologic analysis before vaccination and within 12 weeks after vaccination.

Disease activity was measured using six core set criteria for juvenile arthritis disease activity: physician global assessment, the well-being and disability scales of the Childhood Health Assessment Questionnaire, active joints, limited range of motion, and erythrocyte sedimentation rate. Relapse was considered most likely to occur in the month immediately after vaccination, which was defined as the period of vaccine exposure.

For data analysis, the remaining 11 months of the study period were considered the unexposed period.

Patients for which postvaccination blood samples were available were classified into four groups based on medication use. Patients in group 1 used no medication (47); group 2 used NSAID monotherapy (41); and group 3 used low-dose methotrexate (36) or sulfasalazine (7), with or without NSAIDs. Group 4 consisted of patients receiving high-dose methotrexate (15), methotrexate and sulfasalazine combination therapy (2), infliximab (2), etanercept (6), or cyclosporin A (1), with or without NSAIDs.

Disease activity did not worsen following vaccination, and vaccination did not increase the frequency of disease relapse. Over the 12-month study period, 158 relapses occurred in 97 patients, with 10 patients experiencing disease relapse in the month following vaccination. Risk of relapse in the month following vaccination (exposed period) was 6%, compared with an 8% risk of relapse in the remaining 11 months. Comparable results were seen when the exposed period was defined as 2, 3, or 6 months following vaccination.

Serologic analysis was performed on 141 prevaccination samples and 157 postvaccination samples, including 133 paired samples. Anti-MenC total IgG antibodies in serum were measured by an enzyme-linked immunosorbent assay with a lower limit of detection of 0.24 mcg/mL.

Anti-tetanus toxin antibodies were measured using a tetanus toxin-binding inhibition assay with a lower limit of detection of 0.01 IU/mL. Patients were classified as low responders if postvaccination anti-MenC IgG levels were not greater than 2 mcg/ml.

In the overall study population, anti-MenC IgG geometric mean concentrations increased significantly from 0.4 mcg/mL to 28.9 mcg/mL following vaccination. As expected, postvaccination concentrations were lower in medication groups 3 and 4 (18 and 16, respectively), compared with groups 1 and 2 (41 and 47, respectively).

Four patients were considered low responders. Further testing using serum bactericidal assays (SBA) against serogroup C strain was performed using sera from the 4 low responders and 10 randomly selected serum samples from high responders. The four low responders had postvaccination bactericidal titers within the range indicating an effective bactericidal response, and there were no significant difference in SBA titers in the low responders, compared with the high responders.

“The MenC conjugate vaccine does not aggravate JIA disease activity or increase relapse frequency and results in adequate antibody levels, even in patients receiving highly immunosuppressive therapy,” wrote Dr. Zonneveld-Huijssoon and colleagues. Study results showed the MenC conjugate vaccine to be safe and effective for use in children with JIA.

The meningococcal C conjugate vaccine can be safely and effectively administered to children with juvenile idiopathic arthritis, without aggravating disease activity or increasing relapse frequency, according to study results.

In 2002, Dutch health authorities initiated a national campaign to promote vaccination of all children aged 1–19 years against meningococcal serogroup C disease, but guideline recommendations were nonspecific regarding exclusion of patients with autoimmune diseases and patients on immunosuppressive therapy.

Therefore, Dr. Evelien Zonneveld-Huijssoon, of Wilhelmina Children's Hospital at University Medical Center Utrecht (the Netherlands), and colleagues undertook a study to determine whether vaccination exacerbates disease activity in patients with autoimmune disease and to assess the effect of immunosuppressive medication on vaccine efficacy.

Children with juvenile idiopathic arthritis (JIA) were selected as the study population. Investigators monitored JIA disease activity and immune responses before and after inoculation with a meningococcal C (MenC) conjugate vaccine (Arthritis Rheum. 2007;56:639–46).

A total of 234 JIA patients enrolled in the study. All patients were aged 1–19 years and attended one of the five pediatric rheumatology outpatient clinics participating in the study. The majority of the patients were female (65%), and mean disease duration was 5.9 years.

Patients were followed clinically for 6 months before and after vaccination. The primary outcome measure was disease relapse. Regardless of JIA disease activity, each patient received a single intramuscular dose of the vaccine during the national vaccination campaign and reported the vaccination date on a study questionnaire. Patients provided blood samples for serologic analysis before vaccination and within 12 weeks after vaccination.

Disease activity was measured using six core set criteria for juvenile arthritis disease activity: physician global assessment, the well-being and disability scales of the Childhood Health Assessment Questionnaire, active joints, limited range of motion, and erythrocyte sedimentation rate. Relapse was considered most likely to occur in the month immediately after vaccination, which was defined as the period of vaccine exposure.

For data analysis, the remaining 11 months of the study period were considered the unexposed period.

Patients for which postvaccination blood samples were available were classified into four groups based on medication use. Patients in group 1 used no medication (47); group 2 used NSAID monotherapy (41); and group 3 used low-dose methotrexate (36) or sulfasalazine (7), with or without NSAIDs. Group 4 consisted of patients receiving high-dose methotrexate (15), methotrexate and sulfasalazine combination therapy (2), infliximab (2), etanercept (6), or cyclosporin A (1), with or without NSAIDs.

Disease activity did not worsen following vaccination, and vaccination did not increase the frequency of disease relapse. Over the 12-month study period, 158 relapses occurred in 97 patients, with 10 patients experiencing disease relapse in the month following vaccination. Risk of relapse in the month following vaccination (exposed period) was 6%, compared with an 8% risk of relapse in the remaining 11 months. Comparable results were seen when the exposed period was defined as 2, 3, or 6 months following vaccination.

Serologic analysis was performed on 141 prevaccination samples and 157 postvaccination samples, including 133 paired samples. Anti-MenC total IgG antibodies in serum were measured by an enzyme-linked immunosorbent assay with a lower limit of detection of 0.24 mcg/mL.

Anti-tetanus toxin antibodies were measured using a tetanus toxin-binding inhibition assay with a lower limit of detection of 0.01 IU/mL. Patients were classified as low responders if postvaccination anti-MenC IgG levels were not greater than 2 mcg/ml.

In the overall study population, anti-MenC IgG geometric mean concentrations increased significantly from 0.4 mcg/mL to 28.9 mcg/mL following vaccination. As expected, postvaccination concentrations were lower in medication groups 3 and 4 (18 and 16, respectively), compared with groups 1 and 2 (41 and 47, respectively).

Four patients were considered low responders. Further testing using serum bactericidal assays (SBA) against serogroup C strain was performed using sera from the 4 low responders and 10 randomly selected serum samples from high responders. The four low responders had postvaccination bactericidal titers within the range indicating an effective bactericidal response, and there were no significant difference in SBA titers in the low responders, compared with the high responders.

“The MenC conjugate vaccine does not aggravate JIA disease activity or increase relapse frequency and results in adequate antibody levels, even in patients receiving highly immunosuppressive therapy,” wrote Dr. Zonneveld-Huijssoon and colleagues. Study results showed the MenC conjugate vaccine to be safe and effective for use in children with JIA.

The meningococcal C conjugate vaccine can be safely and effectively administered to children with juvenile idiopathic arthritis, without aggravating disease activity or increasing relapse frequency, according to study results.

In 2002, Dutch health authorities initiated a national campaign to promote vaccination of all children aged 1–19 years against meningococcal serogroup C disease, but guideline recommendations were nonspecific regarding exclusion of patients with autoimmune diseases and patients on immunosuppressive therapy.

Therefore, Dr. Evelien Zonneveld-Huijssoon, of Wilhelmina Children's Hospital at University Medical Center Utrecht (the Netherlands), and colleagues undertook a study to determine whether vaccination exacerbates disease activity in patients with autoimmune disease and to assess the effect of immunosuppressive medication on vaccine efficacy.

Children with juvenile idiopathic arthritis (JIA) were selected as the study population. Investigators monitored JIA disease activity and immune responses before and after inoculation with a meningococcal C (MenC) conjugate vaccine (Arthritis Rheum. 2007;56:639–46).

A total of 234 JIA patients enrolled in the study. All patients were aged 1–19 years and attended one of the five pediatric rheumatology outpatient clinics participating in the study. The majority of the patients were female (65%), and mean disease duration was 5.9 years.

Patients were followed clinically for 6 months before and after vaccination. The primary outcome measure was disease relapse. Regardless of JIA disease activity, each patient received a single intramuscular dose of the vaccine during the national vaccination campaign and reported the vaccination date on a study questionnaire. Patients provided blood samples for serologic analysis before vaccination and within 12 weeks after vaccination.

Disease activity was measured using six core set criteria for juvenile arthritis disease activity: physician global assessment, the well-being and disability scales of the Childhood Health Assessment Questionnaire, active joints, limited range of motion, and erythrocyte sedimentation rate. Relapse was considered most likely to occur in the month immediately after vaccination, which was defined as the period of vaccine exposure.

For data analysis, the remaining 11 months of the study period were considered the unexposed period.

Patients for which postvaccination blood samples were available were classified into four groups based on medication use. Patients in group 1 used no medication (47); group 2 used NSAID monotherapy (41); and group 3 used low-dose methotrexate (36) or sulfasalazine (7), with or without NSAIDs. Group 4 consisted of patients receiving high-dose methotrexate (15), methotrexate and sulfasalazine combination therapy (2), infliximab (2), etanercept (6), or cyclosporin A (1), with or without NSAIDs.

Disease activity did not worsen following vaccination, and vaccination did not increase the frequency of disease relapse. Over the 12-month study period, 158 relapses occurred in 97 patients, with 10 patients experiencing disease relapse in the month following vaccination. Risk of relapse in the month following vaccination (exposed period) was 6%, compared with an 8% risk of relapse in the remaining 11 months. Comparable results were seen when the exposed period was defined as 2, 3, or 6 months following vaccination.

Serologic analysis was performed on 141 prevaccination samples and 157 postvaccination samples, including 133 paired samples. Anti-MenC total IgG antibodies in serum were measured by an enzyme-linked immunosorbent assay with a lower limit of detection of 0.24 mcg/mL.

Anti-tetanus toxin antibodies were measured using a tetanus toxin-binding inhibition assay with a lower limit of detection of 0.01 IU/mL. Patients were classified as low responders if postvaccination anti-MenC IgG levels were not greater than 2 mcg/ml.

In the overall study population, anti-MenC IgG geometric mean concentrations increased significantly from 0.4 mcg/mL to 28.9 mcg/mL following vaccination. As expected, postvaccination concentrations were lower in medication groups 3 and 4 (18 and 16, respectively), compared with groups 1 and 2 (41 and 47, respectively).

Four patients were considered low responders. Further testing using serum bactericidal assays (SBA) against serogroup C strain was performed using sera from the 4 low responders and 10 randomly selected serum samples from high responders. The four low responders had postvaccination bactericidal titers within the range indicating an effective bactericidal response, and there were no significant difference in SBA titers in the low responders, compared with the high responders.

“The MenC conjugate vaccine does not aggravate JIA disease activity or increase relapse frequency and results in adequate antibody levels, even in patients receiving highly immunosuppressive therapy,” wrote Dr. Zonneveld-Huijssoon and colleagues. Study results showed the MenC conjugate vaccine to be safe and effective for use in children with JIA.

New consensus guidelines could help primary care and emergency medicine physicians better manage community-acquired pneumonia in immunocompetent adults.

A joint committee of the Infectious Diseases Society of America and the American Thoracic Society developed the treatment guidelines, which emphasized that they should be modified according to local epidemiology and susceptibility data (Clin. Infect. Dis. 2007;44:S27–72).

The main differences between the consensus guidelines and earlier management guidelines “center on issues of etiology, the site of care decisions, and diagnosis,” Dr. Lionel A. Mandell, professor of medicine at McMaster University, Hamilton, Ont., and the corresponding author of the guidelines publication, said in an interview.

“In terms of etiology, community-acquired MRSA [methicillin-resistant Staphylococcus aureus] has now become an issue. For the site of care decision, the CURB-65 [confusion, uremia, respiratory rate, low blood pressure, age 65 years or greater] criteria are now recommended as well as the PSI [Pneumonia Severity Index] criteria.”

▸ Site of care selection. Assessment of disease severity is the most critical initial decision in management of community-acquired pneumonia (CAP), with an immediate effect on the site of care selection. The guidelines identify the site of care decision as one area in which CAP management could be improved. To assist clinicians in evaluating CAP disease severity and determining the most appropriate site of care, the guidelines recommend the use of severity of illness scores such as CURB-65 and PSI. The three site of care options are outpatient treatment, hospitalization in a medical ward, or admission to an ICU.

▸ ICU admission. The guidelines offer a new set of criteria for the ICU admission decision, while retaining the format of the earlier ATS guidelines. They distinguish between patients meeting major admission criteria (strong recommendation for ICU admission) and those meeting three or more minor admission criteria (moderate recommendation).

Direct admission to an ICU is strongly recommended for patients in septic shock requiring vasopressors or with acute respiratory failure requiring mechanical ventilation. Direct admission is moderately recommended for patients meeting at least three of the following criteria: respiratory rate of 30 breaths/min or higher, arterial oxygen pressure/fraction of inspired oxygen ratio (PaO2/FiO2) of 250 or lower, multilobar infiltrates, confusion/disorientation, BUN level of 20 mg/dL or higher, WBC count less than 4,000 cells/mcL, platelet count less than 100,000 cells/mcL, core temperature below 36° C, and hypotension requiring aggressive fluid resuscitation.

▸ Antibiotics. Empirical antibiotic recommendations do not differ substantially from those in previous guidelines. Additional evidence supports combination antibiotic therapy for severe CAP, and ertapenem is now included as a β-lactam alternative recommended in some circumstances.

▸ Diagnosis and testing. Diagnosis of pneumonia is made based on clinical symptoms and evidence of an infiltrate in the lungs, usually from a chest radiograph or other imaging technique. The issue of diagnostic testing to determine etiology remains controversial. “Blood cultures and Gram stain and culture of respiratory secretions are not recommended for all hospital admissions,” Dr. Mandell said. If the clinician suspects infection with specific pathogens that would be covered more appropriately by a change in the empirical antibiotic regimen, then testing for CAP etiology is recommended. If sputum samples are collected, ideally the samples should be obtained before antibiotic therapy is initiated. Gram stains of sputum samples may offer the twofold benefit of guiding initial antimicrobial therapy and possibly validating later sputum culture results.

Severe CAP is an indication for blood cultures, because of the increased possibility that an unusual pathogen may be detected. Pretreatment blood and sputum cultures also are appropriate for hospitalized patients with risk factors such as asplenia, which would lead to an inability to clear bacteremia, or with comorbid conditions associated with increased likelihood of bacteremia with CAP.

The guidelines are available free at www.journals.uchicago.edu/CID/journal/issues/v44nS2/41620/41620.html

New consensus guidelines could help primary care and emergency medicine physicians better manage community-acquired pneumonia in immunocompetent adults.

A joint committee of the Infectious Diseases Society of America and the American Thoracic Society developed the treatment guidelines, which emphasized that they should be modified according to local epidemiology and susceptibility data (Clin. Infect. Dis. 2007;44:S27–72).

The main differences between the consensus guidelines and earlier management guidelines “center on issues of etiology, the site of care decisions, and diagnosis,” Dr. Lionel A. Mandell, professor of medicine at McMaster University, Hamilton, Ont., and the corresponding author of the guidelines publication, said in an interview.

“In terms of etiology, community-acquired MRSA [methicillin-resistant Staphylococcus aureus] has now become an issue. For the site of care decision, the CURB-65 [confusion, uremia, respiratory rate, low blood pressure, age 65 years or greater] criteria are now recommended as well as the PSI [Pneumonia Severity Index] criteria.”

▸ Site of care selection. Assessment of disease severity is the most critical initial decision in management of community-acquired pneumonia (CAP), with an immediate effect on the site of care selection. The guidelines identify the site of care decision as one area in which CAP management could be improved. To assist clinicians in evaluating CAP disease severity and determining the most appropriate site of care, the guidelines recommend the use of severity of illness scores such as CURB-65 and PSI. The three site of care options are outpatient treatment, hospitalization in a medical ward, or admission to an ICU.

▸ ICU admission. The guidelines offer a new set of criteria for the ICU admission decision, while retaining the format of the earlier ATS guidelines. They distinguish between patients meeting major admission criteria (strong recommendation for ICU admission) and those meeting three or more minor admission criteria (moderate recommendation).

Direct admission to an ICU is strongly recommended for patients in septic shock requiring vasopressors or with acute respiratory failure requiring mechanical ventilation. Direct admission is moderately recommended for patients meeting at least three of the following criteria: respiratory rate of 30 breaths/min or higher, arterial oxygen pressure/fraction of inspired oxygen ratio (PaO2/FiO2) of 250 or lower, multilobar infiltrates, confusion/disorientation, BUN level of 20 mg/dL or higher, WBC count less than 4,000 cells/mcL, platelet count less than 100,000 cells/mcL, core temperature below 36° C, and hypotension requiring aggressive fluid resuscitation.

▸ Antibiotics. Empirical antibiotic recommendations do not differ substantially from those in previous guidelines. Additional evidence supports combination antibiotic therapy for severe CAP, and ertapenem is now included as a β-lactam alternative recommended in some circumstances.

▸ Diagnosis and testing. Diagnosis of pneumonia is made based on clinical symptoms and evidence of an infiltrate in the lungs, usually from a chest radiograph or other imaging technique. The issue of diagnostic testing to determine etiology remains controversial. “Blood cultures and Gram stain and culture of respiratory secretions are not recommended for all hospital admissions,” Dr. Mandell said. If the clinician suspects infection with specific pathogens that would be covered more appropriately by a change in the empirical antibiotic regimen, then testing for CAP etiology is recommended. If sputum samples are collected, ideally the samples should be obtained before antibiotic therapy is initiated. Gram stains of sputum samples may offer the twofold benefit of guiding initial antimicrobial therapy and possibly validating later sputum culture results.

Severe CAP is an indication for blood cultures, because of the increased possibility that an unusual pathogen may be detected. Pretreatment blood and sputum cultures also are appropriate for hospitalized patients with risk factors such as asplenia, which would lead to an inability to clear bacteremia, or with comorbid conditions associated with increased likelihood of bacteremia with CAP.

The guidelines are available free at www.journals.uchicago.edu/CID/journal/issues/v44nS2/41620/41620.html

New consensus guidelines could help primary care and emergency medicine physicians better manage community-acquired pneumonia in immunocompetent adults.

A joint committee of the Infectious Diseases Society of America and the American Thoracic Society developed the treatment guidelines, which emphasized that they should be modified according to local epidemiology and susceptibility data (Clin. Infect. Dis. 2007;44:S27–72).

The main differences between the consensus guidelines and earlier management guidelines “center on issues of etiology, the site of care decisions, and diagnosis,” Dr. Lionel A. Mandell, professor of medicine at McMaster University, Hamilton, Ont., and the corresponding author of the guidelines publication, said in an interview.

“In terms of etiology, community-acquired MRSA [methicillin-resistant Staphylococcus aureus] has now become an issue. For the site of care decision, the CURB-65 [confusion, uremia, respiratory rate, low blood pressure, age 65 years or greater] criteria are now recommended as well as the PSI [Pneumonia Severity Index] criteria.”

▸ Site of care selection. Assessment of disease severity is the most critical initial decision in management of community-acquired pneumonia (CAP), with an immediate effect on the site of care selection. The guidelines identify the site of care decision as one area in which CAP management could be improved. To assist clinicians in evaluating CAP disease severity and determining the most appropriate site of care, the guidelines recommend the use of severity of illness scores such as CURB-65 and PSI. The three site of care options are outpatient treatment, hospitalization in a medical ward, or admission to an ICU.

▸ ICU admission. The guidelines offer a new set of criteria for the ICU admission decision, while retaining the format of the earlier ATS guidelines. They distinguish between patients meeting major admission criteria (strong recommendation for ICU admission) and those meeting three or more minor admission criteria (moderate recommendation).

Direct admission to an ICU is strongly recommended for patients in septic shock requiring vasopressors or with acute respiratory failure requiring mechanical ventilation. Direct admission is moderately recommended for patients meeting at least three of the following criteria: respiratory rate of 30 breaths/min or higher, arterial oxygen pressure/fraction of inspired oxygen ratio (PaO2/FiO2) of 250 or lower, multilobar infiltrates, confusion/disorientation, BUN level of 20 mg/dL or higher, WBC count less than 4,000 cells/mcL, platelet count less than 100,000 cells/mcL, core temperature below 36° C, and hypotension requiring aggressive fluid resuscitation.

▸ Antibiotics. Empirical antibiotic recommendations do not differ substantially from those in previous guidelines. Additional evidence supports combination antibiotic therapy for severe CAP, and ertapenem is now included as a β-lactam alternative recommended in some circumstances.

▸ Diagnosis and testing. Diagnosis of pneumonia is made based on clinical symptoms and evidence of an infiltrate in the lungs, usually from a chest radiograph or other imaging technique. The issue of diagnostic testing to determine etiology remains controversial. “Blood cultures and Gram stain and culture of respiratory secretions are not recommended for all hospital admissions,” Dr. Mandell said. If the clinician suspects infection with specific pathogens that would be covered more appropriately by a change in the empirical antibiotic regimen, then testing for CAP etiology is recommended. If sputum samples are collected, ideally the samples should be obtained before antibiotic therapy is initiated. Gram stains of sputum samples may offer the twofold benefit of guiding initial antimicrobial therapy and possibly validating later sputum culture results.

Severe CAP is an indication for blood cultures, because of the increased possibility that an unusual pathogen may be detected. Pretreatment blood and sputum cultures also are appropriate for hospitalized patients with risk factors such as asplenia, which would lead to an inability to clear bacteremia, or with comorbid conditions associated with increased likelihood of bacteremia with CAP.

The guidelines are available free at www.journals.uchicago.edu/CID/journal/issues/v44nS2/41620/41620.html

Readministration of infliximab was generally safe and effective in patients with ankylosing spondylitis who had previously discontinued treatment, reported Dr. Xenofon Baraliakos and colleagues.

Dr. Baraliakos, of Rheumazentrum Ruhrgebiet in Herne, Germany, and colleagues designed a study to evaluate the safety and efficacy of infliximab readministration in patients with ankylosing spondylitis who experienced clinical relapse following infliximab withdrawal (J. Rheumatol. 2007 Feb. 1; [Epub ahead of print]). The study population consisted of 42 patients with ankylosing spondylitis who had completed a 3-year, open-label extension study of continuous infliximab therapy administered by infusion at a dose of 5 mg/kg every 6 weeks.

Patients discontinued infliximab at the end of the third year of the open-label extension study. The date of infliximab withdrawal was defined as timepoint (TP) 1. Patients were assessed every 6 weeks after infliximab withdrawal for signs of disease flare, the investigators reported. Clinical relapse was defined by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of 4 or greater and a physician's global assessment score of 4 or greater. Patients who experienced clinical relapse were reinfused with infliximab at a dose of 5 mg/kg. The time of clinical relapse was defined as TP2.

Patients were reinfused every 6 weeks after TP2 for the duration of the study. Clinical data were obtained at each visit throughout the study. Study-specific data were collected at the time of infliximab withdrawal, at the time of clinical relapse, and at 24 and 48 weeks after TP2.

Of the 42 patients who enrolled in the study, one remained in clinical remission 48 weeks after infliximab withdrawal, the investigators noted. The remaining 41 patients experienced clinical relapse and were reinfused. One patient, who received eight infusions, dropped out of the study because of repeated local infections.

Infliximab treatment can induce antibodies to infliximab, resulting in the possible loss of clinical efficacy, they noted. Due to measurement difficulties, antibody assays were regarded as inconclusive in patients who had detectable serum levels of infliximab. Of the 42 patients, 27 (64.3%) provided blood samples at the time of infliximab withdrawal, and 35 (83.3%) provided blood samples at clinical relapse. High serum levels of infliximab were detected in 24 (88.9%) of the 27 patients who provided blood samples at infliximab withdrawal, while high levels were detected in 18 patients (51.4%) who provided blood samples at clinical relapse.

One patient showed antibodies to infliximab at 6 weeks after withdrawal, despite an initial favorable response during the previous 3-year study, and no clinical relapse until 24 weeks. This patient withdrew from the study after eight infusions because of repeated local infections.

Among the patients who completed the study after infliximab readministration, mean BASDAI scores increased from 2.5 at the time of infliximab withdrawal to 6.0 at the time of clinical relapse. Mean BASDAI scores decreased following infliximab readministration, to mean values of 2.7 at week 24 to 2.6 at week 48. Median C-reactive protein levels increased from 1.0 at infliximab withdrawal to 11.2 at clinical relapse, dropping again after infliximab readministration to 1.6 at week 24 and 1.8 at week 48. Erythrocyte sedimentation rate showed a similar pattern, rising from median levels of 8 at infliximab withdrawal, to 24 at clinical relapse, and decreasing to 6 and 11 at weeks 24 and 48, respectively.

The authors acknowledged receiving research support from Centocor, the manufacturer of Remicade (infliximab).

Infliximab readministration after relapse lowered BASDAI scores, CRP levels, and ESRs. DR. BARALIAKOS

Readministration of infliximab was generally safe and effective in patients with ankylosing spondylitis who had previously discontinued treatment, reported Dr. Xenofon Baraliakos and colleagues.

Dr. Baraliakos, of Rheumazentrum Ruhrgebiet in Herne, Germany, and colleagues designed a study to evaluate the safety and efficacy of infliximab readministration in patients with ankylosing spondylitis who experienced clinical relapse following infliximab withdrawal (J. Rheumatol. 2007 Feb. 1; [Epub ahead of print]). The study population consisted of 42 patients with ankylosing spondylitis who had completed a 3-year, open-label extension study of continuous infliximab therapy administered by infusion at a dose of 5 mg/kg every 6 weeks.

Patients discontinued infliximab at the end of the third year of the open-label extension study. The date of infliximab withdrawal was defined as timepoint (TP) 1. Patients were assessed every 6 weeks after infliximab withdrawal for signs of disease flare, the investigators reported. Clinical relapse was defined by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of 4 or greater and a physician's global assessment score of 4 or greater. Patients who experienced clinical relapse were reinfused with infliximab at a dose of 5 mg/kg. The time of clinical relapse was defined as TP2.

Patients were reinfused every 6 weeks after TP2 for the duration of the study. Clinical data were obtained at each visit throughout the study. Study-specific data were collected at the time of infliximab withdrawal, at the time of clinical relapse, and at 24 and 48 weeks after TP2.

Of the 42 patients who enrolled in the study, one remained in clinical remission 48 weeks after infliximab withdrawal, the investigators noted. The remaining 41 patients experienced clinical relapse and were reinfused. One patient, who received eight infusions, dropped out of the study because of repeated local infections.

Infliximab treatment can induce antibodies to infliximab, resulting in the possible loss of clinical efficacy, they noted. Due to measurement difficulties, antibody assays were regarded as inconclusive in patients who had detectable serum levels of infliximab. Of the 42 patients, 27 (64.3%) provided blood samples at the time of infliximab withdrawal, and 35 (83.3%) provided blood samples at clinical relapse. High serum levels of infliximab were detected in 24 (88.9%) of the 27 patients who provided blood samples at infliximab withdrawal, while high levels were detected in 18 patients (51.4%) who provided blood samples at clinical relapse.

One patient showed antibodies to infliximab at 6 weeks after withdrawal, despite an initial favorable response during the previous 3-year study, and no clinical relapse until 24 weeks. This patient withdrew from the study after eight infusions because of repeated local infections.

Among the patients who completed the study after infliximab readministration, mean BASDAI scores increased from 2.5 at the time of infliximab withdrawal to 6.0 at the time of clinical relapse. Mean BASDAI scores decreased following infliximab readministration, to mean values of 2.7 at week 24 to 2.6 at week 48. Median C-reactive protein levels increased from 1.0 at infliximab withdrawal to 11.2 at clinical relapse, dropping again after infliximab readministration to 1.6 at week 24 and 1.8 at week 48. Erythrocyte sedimentation rate showed a similar pattern, rising from median levels of 8 at infliximab withdrawal, to 24 at clinical relapse, and decreasing to 6 and 11 at weeks 24 and 48, respectively.

The authors acknowledged receiving research support from Centocor, the manufacturer of Remicade (infliximab).

Infliximab readministration after relapse lowered BASDAI scores, CRP levels, and ESRs. DR. BARALIAKOS

Readministration of infliximab was generally safe and effective in patients with ankylosing spondylitis who had previously discontinued treatment, reported Dr. Xenofon Baraliakos and colleagues.

Dr. Baraliakos, of Rheumazentrum Ruhrgebiet in Herne, Germany, and colleagues designed a study to evaluate the safety and efficacy of infliximab readministration in patients with ankylosing spondylitis who experienced clinical relapse following infliximab withdrawal (J. Rheumatol. 2007 Feb. 1; [Epub ahead of print]). The study population consisted of 42 patients with ankylosing spondylitis who had completed a 3-year, open-label extension study of continuous infliximab therapy administered by infusion at a dose of 5 mg/kg every 6 weeks.

Patients discontinued infliximab at the end of the third year of the open-label extension study. The date of infliximab withdrawal was defined as timepoint (TP) 1. Patients were assessed every 6 weeks after infliximab withdrawal for signs of disease flare, the investigators reported. Clinical relapse was defined by a Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of 4 or greater and a physician's global assessment score of 4 or greater. Patients who experienced clinical relapse were reinfused with infliximab at a dose of 5 mg/kg. The time of clinical relapse was defined as TP2.

Patients were reinfused every 6 weeks after TP2 for the duration of the study. Clinical data were obtained at each visit throughout the study. Study-specific data were collected at the time of infliximab withdrawal, at the time of clinical relapse, and at 24 and 48 weeks after TP2.

Of the 42 patients who enrolled in the study, one remained in clinical remission 48 weeks after infliximab withdrawal, the investigators noted. The remaining 41 patients experienced clinical relapse and were reinfused. One patient, who received eight infusions, dropped out of the study because of repeated local infections.

Infliximab treatment can induce antibodies to infliximab, resulting in the possible loss of clinical efficacy, they noted. Due to measurement difficulties, antibody assays were regarded as inconclusive in patients who had detectable serum levels of infliximab. Of the 42 patients, 27 (64.3%) provided blood samples at the time of infliximab withdrawal, and 35 (83.3%) provided blood samples at clinical relapse. High serum levels of infliximab were detected in 24 (88.9%) of the 27 patients who provided blood samples at infliximab withdrawal, while high levels were detected in 18 patients (51.4%) who provided blood samples at clinical relapse.

One patient showed antibodies to infliximab at 6 weeks after withdrawal, despite an initial favorable response during the previous 3-year study, and no clinical relapse until 24 weeks. This patient withdrew from the study after eight infusions because of repeated local infections.

Among the patients who completed the study after infliximab readministration, mean BASDAI scores increased from 2.5 at the time of infliximab withdrawal to 6.0 at the time of clinical relapse. Mean BASDAI scores decreased following infliximab readministration, to mean values of 2.7 at week 24 to 2.6 at week 48. Median C-reactive protein levels increased from 1.0 at infliximab withdrawal to 11.2 at clinical relapse, dropping again after infliximab readministration to 1.6 at week 24 and 1.8 at week 48. Erythrocyte sedimentation rate showed a similar pattern, rising from median levels of 8 at infliximab withdrawal, to 24 at clinical relapse, and decreasing to 6 and 11 at weeks 24 and 48, respectively.

The authors acknowledged receiving research support from Centocor, the manufacturer of Remicade (infliximab).

Infliximab readministration after relapse lowered BASDAI scores, CRP levels, and ESRs. DR. BARALIAKOS

As an incentive for pharmaceutical companies to conduct clinical trials in children, the Pediatric Exclusivity Program yields variable results, ranging from a generous economic net gain to a net loss, according to a study by Dr. Jennifer Li of Duke Clinical Research Institute, Durham, N.C., and colleagues (JAMA 2007;297:480–8).

Most drugs receive marketing approval in the United States based on clinical trials performed only in an adult population, although the drugs are often used to treat children. The Pediatric Exclusivity Program was designed to encourage pharmaceutical companies to obtain data concerning dosing, safety, and efficacy of marketed drugs in children. Written requests from the Food and Drug Administration specify the number of studies, the indication, sample sizes, and trial designs. In exchange for performing the requested pediatric studies, the pharmaceutical company receives an additional 6 months of marketing exclusivity.

The Best Pharmaceuticals for Children Act of 2002, which created the Pediatric Exclusivity Program, is due for renewal this year. However, despite its success in generating much-needed data on safety and efficacy of drugs given to children, the program has been criticized for providing “windfall” profits to the pharmaceutical industry. Dr. Li and her colleagues evaluated the economic return from marketing exclusivity in a subset of nine drugs that were granted pediatric exclusivity.

During 2002–2004, a total of 59 products received pediatric exclusivity. Of these, 13 (22%) were considered “blockbuster” drugs, with annual sales in the United States in excess of $1 billion. Median annual sales revenue from the 59 products was considerably lower, at $181.3 million, and 23 products had annual sales revenue under $150 million.

The investigators classified the 59 products into nine therapeutic areas and selected one drug from each category for evaluation.

The indications for the nine selected drugs were asthma, tumors, attention-deficit/hyperactivity disorder, diabetes mellitus, gastroesophageal reflux, bacterial infection, and bone mineralization. The selection was heavily weighted toward products that were expected to yield a high economic return, with five “blockbusters” among the nine drugs.

Costs to the pharmaceutical companies in coordinating the clinical trials were estimated from information culled from the final clinical study reports. The estimated costs did not include costs of regulatory filings, costs of juvenile preclinical studies, or costs associated with development of special formulations for pediatric use.

Estimates of after-tax cash inflow over a 6-month period of extended patent protection were extrapolated from market sales data from the previous 3 years. For each of the nine drugs, the investigators calculated the net economic return by subtracting the estimated after-tax cash outflow resulting from the requested pediatric trials from the after-tax cash inflow projected over a 6-month period of extended patent protection.

In the group of nine drugs, 16 efficacy studies, 10 pharmacokinetic studies, and 1 safety study were performed in response to written requests. Median cost per written request was estimated to be $12.3 million (range, $5.1 million-$43.8 million).

Eight of the nine drugs underwent a labeling change as a result of the clinical trials conducted under pediatric exclusivity. “Importantly, several were associated with substantial safety concerns and lack of effectiveness in the pediatric population,” wrote Dr. Li and colleagues.

For 6 months' market exclusivity, the median net economic benefit for the nine drugs was estimated to be $134,265,456, ranging from a loss of $8,946,033 to a gain of $507,899,374, with a net return:cost ratio ranging from −0.68 to 73.63. With a 3-month market exclusivity, the median net economic return decreased to $64,041,833, ranging from a loss of $11,088,214 to a gain of $250,500,635. The net return:cost ratio decreased to a range of −0.84 to 36.31.

The investigators predicted that the reduction of marketing protection from 6 to 3 months would likely dissuade pharmaceutical companies from requesting pediatric exclusivity for products that were unlikely to generate a high economic return.

As an incentive for pharmaceutical companies to conduct clinical trials in children, the Pediatric Exclusivity Program yields variable results, ranging from a generous economic net gain to a net loss, according to a study by Dr. Jennifer Li of Duke Clinical Research Institute, Durham, N.C., and colleagues (JAMA 2007;297:480–8).

Most drugs receive marketing approval in the United States based on clinical trials performed only in an adult population, although the drugs are often used to treat children. The Pediatric Exclusivity Program was designed to encourage pharmaceutical companies to obtain data concerning dosing, safety, and efficacy of marketed drugs in children. Written requests from the Food and Drug Administration specify the number of studies, the indication, sample sizes, and trial designs. In exchange for performing the requested pediatric studies, the pharmaceutical company receives an additional 6 months of marketing exclusivity.

The Best Pharmaceuticals for Children Act of 2002, which created the Pediatric Exclusivity Program, is due for renewal this year. However, despite its success in generating much-needed data on safety and efficacy of drugs given to children, the program has been criticized for providing “windfall” profits to the pharmaceutical industry. Dr. Li and her colleagues evaluated the economic return from marketing exclusivity in a subset of nine drugs that were granted pediatric exclusivity.

During 2002–2004, a total of 59 products received pediatric exclusivity. Of these, 13 (22%) were considered “blockbuster” drugs, with annual sales in the United States in excess of $1 billion. Median annual sales revenue from the 59 products was considerably lower, at $181.3 million, and 23 products had annual sales revenue under $150 million.

The investigators classified the 59 products into nine therapeutic areas and selected one drug from each category for evaluation.

The indications for the nine selected drugs were asthma, tumors, attention-deficit/hyperactivity disorder, diabetes mellitus, gastroesophageal reflux, bacterial infection, and bone mineralization. The selection was heavily weighted toward products that were expected to yield a high economic return, with five “blockbusters” among the nine drugs.

Costs to the pharmaceutical companies in coordinating the clinical trials were estimated from information culled from the final clinical study reports. The estimated costs did not include costs of regulatory filings, costs of juvenile preclinical studies, or costs associated with development of special formulations for pediatric use.

Estimates of after-tax cash inflow over a 6-month period of extended patent protection were extrapolated from market sales data from the previous 3 years. For each of the nine drugs, the investigators calculated the net economic return by subtracting the estimated after-tax cash outflow resulting from the requested pediatric trials from the after-tax cash inflow projected over a 6-month period of extended patent protection.

In the group of nine drugs, 16 efficacy studies, 10 pharmacokinetic studies, and 1 safety study were performed in response to written requests. Median cost per written request was estimated to be $12.3 million (range, $5.1 million-$43.8 million).

Eight of the nine drugs underwent a labeling change as a result of the clinical trials conducted under pediatric exclusivity. “Importantly, several were associated with substantial safety concerns and lack of effectiveness in the pediatric population,” wrote Dr. Li and colleagues.

For 6 months' market exclusivity, the median net economic benefit for the nine drugs was estimated to be $134,265,456, ranging from a loss of $8,946,033 to a gain of $507,899,374, with a net return:cost ratio ranging from −0.68 to 73.63. With a 3-month market exclusivity, the median net economic return decreased to $64,041,833, ranging from a loss of $11,088,214 to a gain of $250,500,635. The net return:cost ratio decreased to a range of −0.84 to 36.31.

The investigators predicted that the reduction of marketing protection from 6 to 3 months would likely dissuade pharmaceutical companies from requesting pediatric exclusivity for products that were unlikely to generate a high economic return.

As an incentive for pharmaceutical companies to conduct clinical trials in children, the Pediatric Exclusivity Program yields variable results, ranging from a generous economic net gain to a net loss, according to a study by Dr. Jennifer Li of Duke Clinical Research Institute, Durham, N.C., and colleagues (JAMA 2007;297:480–8).

Most drugs receive marketing approval in the United States based on clinical trials performed only in an adult population, although the drugs are often used to treat children. The Pediatric Exclusivity Program was designed to encourage pharmaceutical companies to obtain data concerning dosing, safety, and efficacy of marketed drugs in children. Written requests from the Food and Drug Administration specify the number of studies, the indication, sample sizes, and trial designs. In exchange for performing the requested pediatric studies, the pharmaceutical company receives an additional 6 months of marketing exclusivity.

The Best Pharmaceuticals for Children Act of 2002, which created the Pediatric Exclusivity Program, is due for renewal this year. However, despite its success in generating much-needed data on safety and efficacy of drugs given to children, the program has been criticized for providing “windfall” profits to the pharmaceutical industry. Dr. Li and her colleagues evaluated the economic return from marketing exclusivity in a subset of nine drugs that were granted pediatric exclusivity.

During 2002–2004, a total of 59 products received pediatric exclusivity. Of these, 13 (22%) were considered “blockbuster” drugs, with annual sales in the United States in excess of $1 billion. Median annual sales revenue from the 59 products was considerably lower, at $181.3 million, and 23 products had annual sales revenue under $150 million.

The investigators classified the 59 products into nine therapeutic areas and selected one drug from each category for evaluation.

The indications for the nine selected drugs were asthma, tumors, attention-deficit/hyperactivity disorder, diabetes mellitus, gastroesophageal reflux, bacterial infection, and bone mineralization. The selection was heavily weighted toward products that were expected to yield a high economic return, with five “blockbusters” among the nine drugs.

Costs to the pharmaceutical companies in coordinating the clinical trials were estimated from information culled from the final clinical study reports. The estimated costs did not include costs of regulatory filings, costs of juvenile preclinical studies, or costs associated with development of special formulations for pediatric use.

Estimates of after-tax cash inflow over a 6-month period of extended patent protection were extrapolated from market sales data from the previous 3 years. For each of the nine drugs, the investigators calculated the net economic return by subtracting the estimated after-tax cash outflow resulting from the requested pediatric trials from the after-tax cash inflow projected over a 6-month period of extended patent protection.

In the group of nine drugs, 16 efficacy studies, 10 pharmacokinetic studies, and 1 safety study were performed in response to written requests. Median cost per written request was estimated to be $12.3 million (range, $5.1 million-$43.8 million).

Eight of the nine drugs underwent a labeling change as a result of the clinical trials conducted under pediatric exclusivity. “Importantly, several were associated with substantial safety concerns and lack of effectiveness in the pediatric population,” wrote Dr. Li and colleagues.

For 6 months' market exclusivity, the median net economic benefit for the nine drugs was estimated to be $134,265,456, ranging from a loss of $8,946,033 to a gain of $507,899,374, with a net return:cost ratio ranging from −0.68 to 73.63. With a 3-month market exclusivity, the median net economic return decreased to $64,041,833, ranging from a loss of $11,088,214 to a gain of $250,500,635. The net return:cost ratio decreased to a range of −0.84 to 36.31.

The investigators predicted that the reduction of marketing protection from 6 to 3 months would likely dissuade pharmaceutical companies from requesting pediatric exclusivity for products that were unlikely to generate a high economic return.

Clinical outcomes in pediatric appendectomies performed by pediatric surgeons and general surgeons do not differ significantly, reported Dr. Sherif Emil and Michael Taylor.

“There are no specialty-dependent differences in clinical outcomes for simple or complicated appendicitis,” they said. However, simple appendicitis treated by pediatric surgeons was associated with lower hospital costs (J. Am. Coll. Surg. 2007;204:34–9).

To determine whether specialty-dependent differences exist, Dr. Emil and Mr. Taylor of the University of California, Irvine, evaluated clinical characteristics and surgical outcomes of children treated for appendicitis at Miller Children's Hospital in Long Beach, Calif.

The study was based on a review of the medical charts of 465 patients under age 18 who were treated between January 2002 and May 2004.

During the study period, the hospital staff included 26 general surgeons credentialed to perform open appendectomy in patients at least 6 years old.

Of these, 24 surgeons were also credentialed to perform laparoscopic appendectomy in that patient population. Only three general surgeons were credentialed to perform open appendectomy in patients younger than 6 years, and only one was credentialed to perform laparoscopic appendectomy in patients younger than 6 years old.

The pediatric surgical staff consisted of three fellowship-trained, board-certified pediatric surgeons credentialed to perform both open and laparoscopic appendectomy in patients up to age 21 years.

Two of the pediatric surgeons in the study were in academic practice. The third pediatric surgeon and all 26 of the general surgeons were in private practice.

Rates of misdiagnosis, postoperative readmission, wound infection, intra-abdominal infection, and duration of hospital stay were assessed as primary outcomes.

Hospital charges were assessed as a secondary outcome.

The pediatric surgeons treated two-thirds of the children (304), including all but 1 of the 75 children younger than 6 years.

These 304 cases were distributed equally among the three pediatric surgeons, each of whom performed 50–60 appendectomies annually during the 2-year study period.

Of the 26 general surgeons, only 1 performed more than 10 pediatric appendectomies per year during the study period, and only 4 performed more than 5 per year.

Among the general surgeons, the median number of pediatric appendectomies performed per year was 1 (range, 0–11).

Patients in both groups had similar demographic and clinical characteristics, with a few significant differences.

Pediatric surgeons treated children whose mean age was 8.3 years, vs. 13.2 years for those treated by general surgeons.

Pediatric surgeons also treated a significantly higher percentage of children transferred from other hospitals than did general surgeons (42% vs. 23%) and a higher percentage of patients with complicated appendicitis (54% vs. 33%).

Misdiagnosis rates were 4.3% in the pediatric surgeons' group and 5.6% in the general surgeons' group.

For treatment of simple appendicitis, mean hospital stay was 1.82 days in the pediatric surgeons' group, vs. 1.94 days in the general surgeons' group.

Readmission rates were higher in the general surgeons' group than in the pediatric surgeons' group, both for simple appendicitis (2% vs. 0%, respectively) and for complicated appendicitis (6% vs. 2%, respectively).

Complicated appendicitis was associated with higher wound infection and intra-abdominal infection rates in the general surgeons' group (2% and 4%, respectively) than in the pediatric surgeons' group (0.6% and 1%, respectively), but the differences did not reach statistical significance.

Mean hospital stays for complicated appendicitis were 5.21 days in the pediatric surgeons' group and 4.68 days in the general surgeons' group.

General surgeons used postoperative antibiotics in a significantly higher percentage of simple appendicitis cases than did pediatric surgeons (77% vs. 55%, respectively).

Similarly, general surgeons prescribed oral antibiotics on discharge to a higher percentage of patients than did pediatric surgeons, following in-hospital treatment of simple appendicitis (15% vs. 4%, respectively) or complicated appendicitis (66% vs. 30%, respectively).

Median hospital charges for simple appendicitis were $10,735 for the pediatric surgeons' group vs. $11,613 for the general surgeons' group.

A subset analysis of patients aged 6 years and older showed a trend toward shorter hospital stays in the pediatric surgeons' group than in the general surgeons' group (1.75 days vs. 1.94 days, respectively).

Shorter hospital stays and lower use of antibiotics could account for the lower hospital costs for simple appendicitis treated by pediatric surgeons, the authors said.

Clinical outcomes in pediatric appendectomies performed by pediatric surgeons and general surgeons do not differ significantly, reported Dr. Sherif Emil and Michael Taylor.

“There are no specialty-dependent differences in clinical outcomes for simple or complicated appendicitis,” they said. However, simple appendicitis treated by pediatric surgeons was associated with lower hospital costs (J. Am. Coll. Surg. 2007;204:34–9).

To determine whether specialty-dependent differences exist, Dr. Emil and Mr. Taylor of the University of California, Irvine, evaluated clinical characteristics and surgical outcomes of children treated for appendicitis at Miller Children's Hospital in Long Beach, Calif.

The study was based on a review of the medical charts of 465 patients under age 18 who were treated between January 2002 and May 2004.

During the study period, the hospital staff included 26 general surgeons credentialed to perform open appendectomy in patients at least 6 years old.

Of these, 24 surgeons were also credentialed to perform laparoscopic appendectomy in that patient population. Only three general surgeons were credentialed to perform open appendectomy in patients younger than 6 years, and only one was credentialed to perform laparoscopic appendectomy in patients younger than 6 years old.

The pediatric surgical staff consisted of three fellowship-trained, board-certified pediatric surgeons credentialed to perform both open and laparoscopic appendectomy in patients up to age 21 years.

Two of the pediatric surgeons in the study were in academic practice. The third pediatric surgeon and all 26 of the general surgeons were in private practice.

Rates of misdiagnosis, postoperative readmission, wound infection, intra-abdominal infection, and duration of hospital stay were assessed as primary outcomes.

Hospital charges were assessed as a secondary outcome.

The pediatric surgeons treated two-thirds of the children (304), including all but 1 of the 75 children younger than 6 years.

These 304 cases were distributed equally among the three pediatric surgeons, each of whom performed 50–60 appendectomies annually during the 2-year study period.

Of the 26 general surgeons, only 1 performed more than 10 pediatric appendectomies per year during the study period, and only 4 performed more than 5 per year.

Among the general surgeons, the median number of pediatric appendectomies performed per year was 1 (range, 0–11).

Patients in both groups had similar demographic and clinical characteristics, with a few significant differences.

Pediatric surgeons treated children whose mean age was 8.3 years, vs. 13.2 years for those treated by general surgeons.

Pediatric surgeons also treated a significantly higher percentage of children transferred from other hospitals than did general surgeons (42% vs. 23%) and a higher percentage of patients with complicated appendicitis (54% vs. 33%).

Misdiagnosis rates were 4.3% in the pediatric surgeons' group and 5.6% in the general surgeons' group.

For treatment of simple appendicitis, mean hospital stay was 1.82 days in the pediatric surgeons' group, vs. 1.94 days in the general surgeons' group.

Readmission rates were higher in the general surgeons' group than in the pediatric surgeons' group, both for simple appendicitis (2% vs. 0%, respectively) and for complicated appendicitis (6% vs. 2%, respectively).

Complicated appendicitis was associated with higher wound infection and intra-abdominal infection rates in the general surgeons' group (2% and 4%, respectively) than in the pediatric surgeons' group (0.6% and 1%, respectively), but the differences did not reach statistical significance.

Mean hospital stays for complicated appendicitis were 5.21 days in the pediatric surgeons' group and 4.68 days in the general surgeons' group.

General surgeons used postoperative antibiotics in a significantly higher percentage of simple appendicitis cases than did pediatric surgeons (77% vs. 55%, respectively).

Similarly, general surgeons prescribed oral antibiotics on discharge to a higher percentage of patients than did pediatric surgeons, following in-hospital treatment of simple appendicitis (15% vs. 4%, respectively) or complicated appendicitis (66% vs. 30%, respectively).

Median hospital charges for simple appendicitis were $10,735 for the pediatric surgeons' group vs. $11,613 for the general surgeons' group.

A subset analysis of patients aged 6 years and older showed a trend toward shorter hospital stays in the pediatric surgeons' group than in the general surgeons' group (1.75 days vs. 1.94 days, respectively).

Shorter hospital stays and lower use of antibiotics could account for the lower hospital costs for simple appendicitis treated by pediatric surgeons, the authors said.

Clinical outcomes in pediatric appendectomies performed by pediatric surgeons and general surgeons do not differ significantly, reported Dr. Sherif Emil and Michael Taylor.

“There are no specialty-dependent differences in clinical outcomes for simple or complicated appendicitis,” they said. However, simple appendicitis treated by pediatric surgeons was associated with lower hospital costs (J. Am. Coll. Surg. 2007;204:34–9).

To determine whether specialty-dependent differences exist, Dr. Emil and Mr. Taylor of the University of California, Irvine, evaluated clinical characteristics and surgical outcomes of children treated for appendicitis at Miller Children's Hospital in Long Beach, Calif.

The study was based on a review of the medical charts of 465 patients under age 18 who were treated between January 2002 and May 2004.

During the study period, the hospital staff included 26 general surgeons credentialed to perform open appendectomy in patients at least 6 years old.

Of these, 24 surgeons were also credentialed to perform laparoscopic appendectomy in that patient population. Only three general surgeons were credentialed to perform open appendectomy in patients younger than 6 years, and only one was credentialed to perform laparoscopic appendectomy in patients younger than 6 years old.

The pediatric surgical staff consisted of three fellowship-trained, board-certified pediatric surgeons credentialed to perform both open and laparoscopic appendectomy in patients up to age 21 years.

Two of the pediatric surgeons in the study were in academic practice. The third pediatric surgeon and all 26 of the general surgeons were in private practice.

Rates of misdiagnosis, postoperative readmission, wound infection, intra-abdominal infection, and duration of hospital stay were assessed as primary outcomes.

Hospital charges were assessed as a secondary outcome.

The pediatric surgeons treated two-thirds of the children (304), including all but 1 of the 75 children younger than 6 years.

These 304 cases were distributed equally among the three pediatric surgeons, each of whom performed 50–60 appendectomies annually during the 2-year study period.

Of the 26 general surgeons, only 1 performed more than 10 pediatric appendectomies per year during the study period, and only 4 performed more than 5 per year.

Among the general surgeons, the median number of pediatric appendectomies performed per year was 1 (range, 0–11).

Patients in both groups had similar demographic and clinical characteristics, with a few significant differences.

Pediatric surgeons treated children whose mean age was 8.3 years, vs. 13.2 years for those treated by general surgeons.

Pediatric surgeons also treated a significantly higher percentage of children transferred from other hospitals than did general surgeons (42% vs. 23%) and a higher percentage of patients with complicated appendicitis (54% vs. 33%).

Misdiagnosis rates were 4.3% in the pediatric surgeons' group and 5.6% in the general surgeons' group.

For treatment of simple appendicitis, mean hospital stay was 1.82 days in the pediatric surgeons' group, vs. 1.94 days in the general surgeons' group.

Readmission rates were higher in the general surgeons' group than in the pediatric surgeons' group, both for simple appendicitis (2% vs. 0%, respectively) and for complicated appendicitis (6% vs. 2%, respectively).

Complicated appendicitis was associated with higher wound infection and intra-abdominal infection rates in the general surgeons' group (2% and 4%, respectively) than in the pediatric surgeons' group (0.6% and 1%, respectively), but the differences did not reach statistical significance.

Mean hospital stays for complicated appendicitis were 5.21 days in the pediatric surgeons' group and 4.68 days in the general surgeons' group.

General surgeons used postoperative antibiotics in a significantly higher percentage of simple appendicitis cases than did pediatric surgeons (77% vs. 55%, respectively).

Similarly, general surgeons prescribed oral antibiotics on discharge to a higher percentage of patients than did pediatric surgeons, following in-hospital treatment of simple appendicitis (15% vs. 4%, respectively) or complicated appendicitis (66% vs. 30%, respectively).

Median hospital charges for simple appendicitis were $10,735 for the pediatric surgeons' group vs. $11,613 for the general surgeons' group.

A subset analysis of patients aged 6 years and older showed a trend toward shorter hospital stays in the pediatric surgeons' group than in the general surgeons' group (1.75 days vs. 1.94 days, respectively).

Shorter hospital stays and lower use of antibiotics could account for the lower hospital costs for simple appendicitis treated by pediatric surgeons, the authors said.

The strategy of reimmunizing children following standard chemotherapy or hematopoietic stem cell transplantation for childhood cancer appears effective in protecting a vulnerable population against vaccine-preventable childhood diseases, according to two studies reported in Clinical Infectious Diseases.

“The main advantages of the strategy are its simplicity and the fact that it avoids the expense and difficulty of individual testing of antibodies against vaccine antigens,” Dr. Julia Chisholm of Great Ormond Street Hospital, London, wrote in an editorial accompanying the studies (Clin. Infect. Dis. 2007;44:643–5).

Dr. Soonie Patel of Royal Marsden Hospital in Sutton (England) and colleagues evaluated revaccination schedules for children after hematopoietic stem cell transplantation (Clin. Infect. Dis. 2007;44:625–34) and after standard chemotherapy for acute leukemia (Clin. Infect. Dis. 2007; 44:635–42).

Vaccines administered in both studies were diphtheria-tetanus-acellular pertussis (DTaP; Infanrix, GlaxoSmithKline), Haemophilus influenzae type b (Hib; Hiberix, GlaxoSmithKline), meningococcus C conjugate (MCC; Meningitec, Wyeth), measles-mumps-rubella (MMR; MMR II, Aventis), and inactivated poliovirus (IPV; Imovax, Aventis Pasteur) vaccines.

Fifty-nine children with acute leukemia were enrolled in the postchemotherapy study. The median age at diagnosis was 5 years (range: 1–16 years), and the median age at vaccination was 8 years (range: 3–18 years). Forty-six children had acute lymphoblastic leukemia (ALL), and 13 children had acute myeloid leukemia (AML). All children had received chemotherapy according to the Medical Research Council of United Kingdom protocols for ALL or AML, as appropriate.

Thirty-eight children were enrolled in the hematopoietic stem cell transplantation (HSCT) after malignancies study, including 8 autologous HSCT recipients and 30 allogenic HSCT recipients. The median age at transplantation was 9 years (range: 2–17 years), and the median age at vaccination was 13 (range: 4–19 years).

To assess vaccine efficacy, investigators calculated the percentage of children with protective immunity after revaccination. Before leukemia treatment or transplantation, all children in both studies had received some vaccines, and some had degrees of protective immunity.

With each of the vaccines, antibody titers increased significantly following vaccination postchemotherapy or post-HSCT. Long-term protective antibody levels were achieved for tetanus toxin in 100% of patients tested in both studies, for Hib in 100% of HSCT patients tested and 93% of leukemia patients tested, and for measles in 100% of HSCT patients tested and 94% of leukemia patients tested. Notably, some of the HSCT recipients experienced primary vaccine failure with the MMR vaccine, but protection was achieved after the second dose.

All HSCT patients tested and 96% of leukemia patients tested achieved protection against meningococcus C. IPV vaccination resulted in protective titers to all three poliovirus serotypes in 92% of HSCT patients tested and in 85% of leukemia patients tested.

In the HSCT study, 9-month serum samples were available only in a subset of patients for testing antibody levels to tetanus, Hib, poliovirus, and meningococcus C. Results showed that antibody titers had dropped but remained within the protective range. For each of the vaccines, protection persisted after 12 months for most leukemia patients tested.

“Administration of a single vaccine dose 6 months after standard chemotherapy is sufficient to confer protection against common vaccine-preventable diseases in the majority of children treated for childhood leukemia. Similarly, revaccination of pediatric HSCT recipients according to the multiple-dose schedule used in the study provides a high level of protection against these vaccine-preventable diseases,” the investigators concluded.

The strategy of reimmunizing children following standard chemotherapy or hematopoietic stem cell transplantation for childhood cancer appears effective in protecting a vulnerable population against vaccine-preventable childhood diseases, according to two studies reported in Clinical Infectious Diseases.

“The main advantages of the strategy are its simplicity and the fact that it avoids the expense and difficulty of individual testing of antibodies against vaccine antigens,” Dr. Julia Chisholm of Great Ormond Street Hospital, London, wrote in an editorial accompanying the studies (Clin. Infect. Dis. 2007;44:643–5).

Dr. Soonie Patel of Royal Marsden Hospital in Sutton (England) and colleagues evaluated revaccination schedules for children after hematopoietic stem cell transplantation (Clin. Infect. Dis. 2007;44:625–34) and after standard chemotherapy for acute leukemia (Clin. Infect. Dis. 2007; 44:635–42).

Vaccines administered in both studies were diphtheria-tetanus-acellular pertussis (DTaP; Infanrix, GlaxoSmithKline), Haemophilus influenzae type b (Hib; Hiberix, GlaxoSmithKline), meningococcus C conjugate (MCC; Meningitec, Wyeth), measles-mumps-rubella (MMR; MMR II, Aventis), and inactivated poliovirus (IPV; Imovax, Aventis Pasteur) vaccines.

Fifty-nine children with acute leukemia were enrolled in the postchemotherapy study. The median age at diagnosis was 5 years (range: 1–16 years), and the median age at vaccination was 8 years (range: 3–18 years). Forty-six children had acute lymphoblastic leukemia (ALL), and 13 children had acute myeloid leukemia (AML). All children had received chemotherapy according to the Medical Research Council of United Kingdom protocols for ALL or AML, as appropriate.

Thirty-eight children were enrolled in the hematopoietic stem cell transplantation (HSCT) after malignancies study, including 8 autologous HSCT recipients and 30 allogenic HSCT recipients. The median age at transplantation was 9 years (range: 2–17 years), and the median age at vaccination was 13 (range: 4–19 years).

To assess vaccine efficacy, investigators calculated the percentage of children with protective immunity after revaccination. Before leukemia treatment or transplantation, all children in both studies had received some vaccines, and some had degrees of protective immunity.

With each of the vaccines, antibody titers increased significantly following vaccination postchemotherapy or post-HSCT. Long-term protective antibody levels were achieved for tetanus toxin in 100% of patients tested in both studies, for Hib in 100% of HSCT patients tested and 93% of leukemia patients tested, and for measles in 100% of HSCT patients tested and 94% of leukemia patients tested. Notably, some of the HSCT recipients experienced primary vaccine failure with the MMR vaccine, but protection was achieved after the second dose.

All HSCT patients tested and 96% of leukemia patients tested achieved protection against meningococcus C. IPV vaccination resulted in protective titers to all three poliovirus serotypes in 92% of HSCT patients tested and in 85% of leukemia patients tested.

In the HSCT study, 9-month serum samples were available only in a subset of patients for testing antibody levels to tetanus, Hib, poliovirus, and meningococcus C. Results showed that antibody titers had dropped but remained within the protective range. For each of the vaccines, protection persisted after 12 months for most leukemia patients tested.

“Administration of a single vaccine dose 6 months after standard chemotherapy is sufficient to confer protection against common vaccine-preventable diseases in the majority of children treated for childhood leukemia. Similarly, revaccination of pediatric HSCT recipients according to the multiple-dose schedule used in the study provides a high level of protection against these vaccine-preventable diseases,” the investigators concluded.

The strategy of reimmunizing children following standard chemotherapy or hematopoietic stem cell transplantation for childhood cancer appears effective in protecting a vulnerable population against vaccine-preventable childhood diseases, according to two studies reported in Clinical Infectious Diseases.

“The main advantages of the strategy are its simplicity and the fact that it avoids the expense and difficulty of individual testing of antibodies against vaccine antigens,” Dr. Julia Chisholm of Great Ormond Street Hospital, London, wrote in an editorial accompanying the studies (Clin. Infect. Dis. 2007;44:643–5).

Dr. Soonie Patel of Royal Marsden Hospital in Sutton (England) and colleagues evaluated revaccination schedules for children after hematopoietic stem cell transplantation (Clin. Infect. Dis. 2007;44:625–34) and after standard chemotherapy for acute leukemia (Clin. Infect. Dis. 2007; 44:635–42).

Vaccines administered in both studies were diphtheria-tetanus-acellular pertussis (DTaP; Infanrix, GlaxoSmithKline), Haemophilus influenzae type b (Hib; Hiberix, GlaxoSmithKline), meningococcus C conjugate (MCC; Meningitec, Wyeth), measles-mumps-rubella (MMR; MMR II, Aventis), and inactivated poliovirus (IPV; Imovax, Aventis Pasteur) vaccines.

Fifty-nine children with acute leukemia were enrolled in the postchemotherapy study. The median age at diagnosis was 5 years (range: 1–16 years), and the median age at vaccination was 8 years (range: 3–18 years). Forty-six children had acute lymphoblastic leukemia (ALL), and 13 children had acute myeloid leukemia (AML). All children had received chemotherapy according to the Medical Research Council of United Kingdom protocols for ALL or AML, as appropriate.

Thirty-eight children were enrolled in the hematopoietic stem cell transplantation (HSCT) after malignancies study, including 8 autologous HSCT recipients and 30 allogenic HSCT recipients. The median age at transplantation was 9 years (range: 2–17 years), and the median age at vaccination was 13 (range: 4–19 years).

To assess vaccine efficacy, investigators calculated the percentage of children with protective immunity after revaccination. Before leukemia treatment or transplantation, all children in both studies had received some vaccines, and some had degrees of protective immunity.

With each of the vaccines, antibody titers increased significantly following vaccination postchemotherapy or post-HSCT. Long-term protective antibody levels were achieved for tetanus toxin in 100% of patients tested in both studies, for Hib in 100% of HSCT patients tested and 93% of leukemia patients tested, and for measles in 100% of HSCT patients tested and 94% of leukemia patients tested. Notably, some of the HSCT recipients experienced primary vaccine failure with the MMR vaccine, but protection was achieved after the second dose.

All HSCT patients tested and 96% of leukemia patients tested achieved protection against meningococcus C. IPV vaccination resulted in protective titers to all three poliovirus serotypes in 92% of HSCT patients tested and in 85% of leukemia patients tested.

In the HSCT study, 9-month serum samples were available only in a subset of patients for testing antibody levels to tetanus, Hib, poliovirus, and meningococcus C. Results showed that antibody titers had dropped but remained within the protective range. For each of the vaccines, protection persisted after 12 months for most leukemia patients tested.

“Administration of a single vaccine dose 6 months after standard chemotherapy is sufficient to confer protection against common vaccine-preventable diseases in the majority of children treated for childhood leukemia. Similarly, revaccination of pediatric HSCT recipients according to the multiple-dose schedule used in the study provides a high level of protection against these vaccine-preventable diseases,” the investigators concluded.

Older men and women who were once heavy smokers have a significantly higher risk of diabetes and obesity than do nonsmokers or current light smokers, according to Tommi Sulander of Finland's National Public Health Institute, Helsinki, and colleagues.

The investigators examined the associations between smoking status, diabetes, and obesity using data from nationwide biennial surveys conducted in Finland from 1985 to 1995. The study population consisted of 7,482 individuals (3,738 men and 3,744 women) aged 65–79 years.

Survey data were collected by self-report using standardized questionnaires with items concerning weight, smoking status, illnesses, diet, alcohol consumption, and physical activity. Data were analyzed using logistic regression models (Arch. Gerontol. Geriatr. 2006 [Epub doi:10.1016/j.archger.2006.10.007]).

Age was categorized by 5-year intervals. Light smoking was defined as 1–19 cigarettes a day, and heavy smoking was defined as 20 or more cigarettes a day. Smoking status was classified in five categories: nonsmoker, current light smoker, current heavy smoker, ex-light smoker, and ex-heavy smoker. Obesity was defined as a body mass index (kg/m2) of 30 or greater.

Relative to nonsmokers, ex-heavy smokers had higher risks of developing both obesity and diabetes, whereas current light smokers had lower risks for both conditions. In a logistic regression model adjusting only for age and gender, relative obesity risks were 1.38 for ex-heavy smokers and 0.43 for current light smokers. Similarly, relative risks of diabetes were higher for ex-heavy smokers (1.36) and lower for current light smokers (0.51). Rates of obesity and rates of diabetes were comparable among nonsmokers, ex-light smokers, and current heavy smokers.

Older men and women who were once heavy smokers have a significantly higher risk of diabetes and obesity than do nonsmokers or current light smokers, according to Tommi Sulander of Finland's National Public Health Institute, Helsinki, and colleagues.

The investigators examined the associations between smoking status, diabetes, and obesity using data from nationwide biennial surveys conducted in Finland from 1985 to 1995. The study population consisted of 7,482 individuals (3,738 men and 3,744 women) aged 65–79 years.

Survey data were collected by self-report using standardized questionnaires with items concerning weight, smoking status, illnesses, diet, alcohol consumption, and physical activity. Data were analyzed using logistic regression models (Arch. Gerontol. Geriatr. 2006 [Epub doi:10.1016/j.archger.2006.10.007]).

Age was categorized by 5-year intervals. Light smoking was defined as 1–19 cigarettes a day, and heavy smoking was defined as 20 or more cigarettes a day. Smoking status was classified in five categories: nonsmoker, current light smoker, current heavy smoker, ex-light smoker, and ex-heavy smoker. Obesity was defined as a body mass index (kg/m2) of 30 or greater.

Relative to nonsmokers, ex-heavy smokers had higher risks of developing both obesity and diabetes, whereas current light smokers had lower risks for both conditions. In a logistic regression model adjusting only for age and gender, relative obesity risks were 1.38 for ex-heavy smokers and 0.43 for current light smokers. Similarly, relative risks of diabetes were higher for ex-heavy smokers (1.36) and lower for current light smokers (0.51). Rates of obesity and rates of diabetes were comparable among nonsmokers, ex-light smokers, and current heavy smokers.

Older men and women who were once heavy smokers have a significantly higher risk of diabetes and obesity than do nonsmokers or current light smokers, according to Tommi Sulander of Finland's National Public Health Institute, Helsinki, and colleagues.

The investigators examined the associations between smoking status, diabetes, and obesity using data from nationwide biennial surveys conducted in Finland from 1985 to 1995. The study population consisted of 7,482 individuals (3,738 men and 3,744 women) aged 65–79 years.

Survey data were collected by self-report using standardized questionnaires with items concerning weight, smoking status, illnesses, diet, alcohol consumption, and physical activity. Data were analyzed using logistic regression models (Arch. Gerontol. Geriatr. 2006 [Epub doi:10.1016/j.archger.2006.10.007]).

Age was categorized by 5-year intervals. Light smoking was defined as 1–19 cigarettes a day, and heavy smoking was defined as 20 or more cigarettes a day. Smoking status was classified in five categories: nonsmoker, current light smoker, current heavy smoker, ex-light smoker, and ex-heavy smoker. Obesity was defined as a body mass index (kg/m2) of 30 or greater.

Relative to nonsmokers, ex-heavy smokers had higher risks of developing both obesity and diabetes, whereas current light smokers had lower risks for both conditions. In a logistic regression model adjusting only for age and gender, relative obesity risks were 1.38 for ex-heavy smokers and 0.43 for current light smokers. Similarly, relative risks of diabetes were higher for ex-heavy smokers (1.36) and lower for current light smokers (0.51). Rates of obesity and rates of diabetes were comparable among nonsmokers, ex-light smokers, and current heavy smokers.

Concomitant use of abatacept can significantly improve physical and mental health and physical functioning in patients with rheumatoid arthritis who have had an inadequate response to methotrexate treatment, reported Dr. Anthony Russell of the University of Alberta, Edmonton.

Dr. Russell and his colleagues analyzed health-related quality of life data from the Abatacept in Inadequate responders to Methotrexate (AIM) trial, a 1-year, randomized, double-blind, placebo-controlled, phase III trial conducted at 116 sites worldwide.

The AIM trial was designed to evaluate once-monthly abatacept as an adjunct to methotrexate (MTX) for treatment of rheumatoid arthritis (RA) in patients who continued to have active disease despite MTX therapy. An earlier report describes the primary efficacy and safety results of the AIM study (Ann Intern Med 2006;144:865–76). The AIM study population consisted of RA patients who had persistent, active disease despite treatment with MTX for at least 3 months.

Participants also were required to be at least 18 years old; to have had RA for at least 1 year since diagnosis; to have functional status I, II, or III disease; and to have active disease, defined as 10 or more swollen joints, 12 or more tender joints, and C-reactive protein levels of 10 mg/L or higher. Patients were required to maintain a steady dose of MTX for at least 28 days before enrollment.

Patients were not allowed to take any other disease-modifying antirheumatic drugs (DMARDs) during the study, and patients were required to undergo washout of other DMARDs at least 28 days before randomization.

Patients were randomized 2:1 to receive a fixed dose of abatacept (approximately 10 mg/kg) or placebo by intravenous infusion on days 1, 15, and 29 for the first month and every 28 days thereafter for up to 12 months. All patients remained on MTX at a weekly dose of 15 mg or greater throughout the study.

A total of 652 patients participated in the trial, with 433 in the abatacept-MTX group and 219 patients in the placebo-MTX group. The mean age of the patients was 51.5 years, and the mean disease duration was 8.6 years.

Health outcomes were assessed using the Medical Outcomes Study Short Form (SF)-36 Health Survey, consisting of eight scales covering physical and mental health, and the Health Assessment Questionnaire (HAQ), designed to assess physical functioning. Both questionnaires were self-administered. Patients completed the SF-36 at baseline and at months 1, 3, 6, and 12. Patients completed the HAQ at baseline, at days 15 and 29 within the first month of treatment, and every 28 days thereafter.

“[T]he physical functioning of these patients is comparable to that of patients with congestive heart failure in the general U.S. population,” wrote Dr. Russell. In both treatment groups mean baseline scores were approximately one standard deviation below the U.S. population norm for most of the eight subscales of the SF-36.

The mean physical component summary (PCS) scores of the SF-36 were 30.6 for the abatacept-MTX group and 30.7 for the placebo-MTX group at baseline, approximately two SD below the U.S. population norm of 50. Baseline mean scores in the mental component summary (MCS) of the SF-36 were 41.8 in the abatacept-MTX group and 40.8 in the placebo-MTX group, approximately one SD below the U.S. population norm of 50.

Differences between the two treatment groups in quality-of-life measures emerged within the first month of treatment. Relative to the placebo-MTX group, the abatacept-MTX group showed significant improvement by day 29 for five of the eight SF-36 subdomains: self-reported bodily pain, role physical, general health, vitality, and social functioning.

“After 3 months of treatment, the difference between abatacept and placebo widened for all of the SF-36 domains,” reported Dr. Russell (Ann. Rheum. Dis. 2007 [Epub doi: 10.1136/ard.2006.057018]).

For each of the various health outcome categories, investigators calculated the proportion of patients in each treatment group whose score improved by at least 0.5 SD over the 12-month study period. Significant differences were observed in the abatacept-MTX group relative to the placebo-MTX group after 12 months in the proportion of patients who showed improvement in PCS (67.2% vs. 51.1%, respectively) and in HAQ (72.4% vs. 55.2%, respectively).

“Combined abatacept and MTX treatment produces significant improvements across a wide range of health-related quality of life domains in patients with RA,” concluded Dr. Russell.

The project was supported financially by Bristol-Myers Squibb, makers of Orencia (abatacept).

Concomitant use of abatacept can significantly improve physical and mental health and physical functioning in patients with rheumatoid arthritis who have had an inadequate response to methotrexate treatment, reported Dr. Anthony Russell of the University of Alberta, Edmonton.

Dr. Russell and his colleagues analyzed health-related quality of life data from the Abatacept in Inadequate responders to Methotrexate (AIM) trial, a 1-year, randomized, double-blind, placebo-controlled, phase III trial conducted at 116 sites worldwide.

The AIM trial was designed to evaluate once-monthly abatacept as an adjunct to methotrexate (MTX) for treatment of rheumatoid arthritis (RA) in patients who continued to have active disease despite MTX therapy. An earlier report describes the primary efficacy and safety results of the AIM study (Ann Intern Med 2006;144:865–76). The AIM study population consisted of RA patients who had persistent, active disease despite treatment with MTX for at least 3 months.

Participants also were required to be at least 18 years old; to have had RA for at least 1 year since diagnosis; to have functional status I, II, or III disease; and to have active disease, defined as 10 or more swollen joints, 12 or more tender joints, and C-reactive protein levels of 10 mg/L or higher. Patients were required to maintain a steady dose of MTX for at least 28 days before enrollment.

Patients were not allowed to take any other disease-modifying antirheumatic drugs (DMARDs) during the study, and patients were required to undergo washout of other DMARDs at least 28 days before randomization.

Patients were randomized 2:1 to receive a fixed dose of abatacept (approximately 10 mg/kg) or placebo by intravenous infusion on days 1, 15, and 29 for the first month and every 28 days thereafter for up to 12 months. All patients remained on MTX at a weekly dose of 15 mg or greater throughout the study.

A total of 652 patients participated in the trial, with 433 in the abatacept-MTX group and 219 patients in the placebo-MTX group. The mean age of the patients was 51.5 years, and the mean disease duration was 8.6 years.

Health outcomes were assessed using the Medical Outcomes Study Short Form (SF)-36 Health Survey, consisting of eight scales covering physical and mental health, and the Health Assessment Questionnaire (HAQ), designed to assess physical functioning. Both questionnaires were self-administered. Patients completed the SF-36 at baseline and at months 1, 3, 6, and 12. Patients completed the HAQ at baseline, at days 15 and 29 within the first month of treatment, and every 28 days thereafter.

“[T]he physical functioning of these patients is comparable to that of patients with congestive heart failure in the general U.S. population,” wrote Dr. Russell. In both treatment groups mean baseline scores were approximately one standard deviation below the U.S. population norm for most of the eight subscales of the SF-36.

The mean physical component summary (PCS) scores of the SF-36 were 30.6 for the abatacept-MTX group and 30.7 for the placebo-MTX group at baseline, approximately two SD below the U.S. population norm of 50. Baseline mean scores in the mental component summary (MCS) of the SF-36 were 41.8 in the abatacept-MTX group and 40.8 in the placebo-MTX group, approximately one SD below the U.S. population norm of 50.

Differences between the two treatment groups in quality-of-life measures emerged within the first month of treatment. Relative to the placebo-MTX group, the abatacept-MTX group showed significant improvement by day 29 for five of the eight SF-36 subdomains: self-reported bodily pain, role physical, general health, vitality, and social functioning.

“After 3 months of treatment, the difference between abatacept and placebo widened for all of the SF-36 domains,” reported Dr. Russell (Ann. Rheum. Dis. 2007 [Epub doi: 10.1136/ard.2006.057018]).

For each of the various health outcome categories, investigators calculated the proportion of patients in each treatment group whose score improved by at least 0.5 SD over the 12-month study period. Significant differences were observed in the abatacept-MTX group relative to the placebo-MTX group after 12 months in the proportion of patients who showed improvement in PCS (67.2% vs. 51.1%, respectively) and in HAQ (72.4% vs. 55.2%, respectively).

“Combined abatacept and MTX treatment produces significant improvements across a wide range of health-related quality of life domains in patients with RA,” concluded Dr. Russell.

The project was supported financially by Bristol-Myers Squibb, makers of Orencia (abatacept).

Concomitant use of abatacept can significantly improve physical and mental health and physical functioning in patients with rheumatoid arthritis who have had an inadequate response to methotrexate treatment, reported Dr. Anthony Russell of the University of Alberta, Edmonton.

Dr. Russell and his colleagues analyzed health-related quality of life data from the Abatacept in Inadequate responders to Methotrexate (AIM) trial, a 1-year, randomized, double-blind, placebo-controlled, phase III trial conducted at 116 sites worldwide.

The AIM trial was designed to evaluate once-monthly abatacept as an adjunct to methotrexate (MTX) for treatment of rheumatoid arthritis (RA) in patients who continued to have active disease despite MTX therapy. An earlier report describes the primary efficacy and safety results of the AIM study (Ann Intern Med 2006;144:865–76). The AIM study population consisted of RA patients who had persistent, active disease despite treatment with MTX for at least 3 months.

Participants also were required to be at least 18 years old; to have had RA for at least 1 year since diagnosis; to have functional status I, II, or III disease; and to have active disease, defined as 10 or more swollen joints, 12 or more tender joints, and C-reactive protein levels of 10 mg/L or higher. Patients were required to maintain a steady dose of MTX for at least 28 days before enrollment.

Patients were not allowed to take any other disease-modifying antirheumatic drugs (DMARDs) during the study, and patients were required to undergo washout of other DMARDs at least 28 days before randomization.

Patients were randomized 2:1 to receive a fixed dose of abatacept (approximately 10 mg/kg) or placebo by intravenous infusion on days 1, 15, and 29 for the first month and every 28 days thereafter for up to 12 months. All patients remained on MTX at a weekly dose of 15 mg or greater throughout the study.

A total of 652 patients participated in the trial, with 433 in the abatacept-MTX group and 219 patients in the placebo-MTX group. The mean age of the patients was 51.5 years, and the mean disease duration was 8.6 years.

Health outcomes were assessed using the Medical Outcomes Study Short Form (SF)-36 Health Survey, consisting of eight scales covering physical and mental health, and the Health Assessment Questionnaire (HAQ), designed to assess physical functioning. Both questionnaires were self-administered. Patients completed the SF-36 at baseline and at months 1, 3, 6, and 12. Patients completed the HAQ at baseline, at days 15 and 29 within the first month of treatment, and every 28 days thereafter.

“[T]he physical functioning of these patients is comparable to that of patients with congestive heart failure in the general U.S. population,” wrote Dr. Russell. In both treatment groups mean baseline scores were approximately one standard deviation below the U.S. population norm for most of the eight subscales of the SF-36.

The mean physical component summary (PCS) scores of the SF-36 were 30.6 for the abatacept-MTX group and 30.7 for the placebo-MTX group at baseline, approximately two SD below the U.S. population norm of 50. Baseline mean scores in the mental component summary (MCS) of the SF-36 were 41.8 in the abatacept-MTX group and 40.8 in the placebo-MTX group, approximately one SD below the U.S. population norm of 50.

Differences between the two treatment groups in quality-of-life measures emerged within the first month of treatment. Relative to the placebo-MTX group, the abatacept-MTX group showed significant improvement by day 29 for five of the eight SF-36 subdomains: self-reported bodily pain, role physical, general health, vitality, and social functioning.

“After 3 months of treatment, the difference between abatacept and placebo widened for all of the SF-36 domains,” reported Dr. Russell (Ann. Rheum. Dis. 2007 [Epub doi: 10.1136/ard.2006.057018]).

For each of the various health outcome categories, investigators calculated the proportion of patients in each treatment group whose score improved by at least 0.5 SD over the 12-month study period. Significant differences were observed in the abatacept-MTX group relative to the placebo-MTX group after 12 months in the proportion of patients who showed improvement in PCS (67.2% vs. 51.1%, respectively) and in HAQ (72.4% vs. 55.2%, respectively).

“Combined abatacept and MTX treatment produces significant improvements across a wide range of health-related quality of life domains in patients with RA,” concluded Dr. Russell.

The project was supported financially by Bristol-Myers Squibb, makers of Orencia (abatacept).

MENDOZA, ARGENTINA – When it comes to adolescents with depression, psychiatrists would do well to tailor treatment to the individual needs of each patient, Dr. Harold I. Eist said at the 6th World Congress on Depressive Disorders.

Adolescence is a turbulent period with enormous biologic, psychological, and social changes, said Dr. Eist, a psychiatrist in private practice in Bethesda, Md., and a past president of the American Psychiatric Association. The brain of the adolescent is immature–“an impulsive, aggressive, thrill-seeking brain,” he said. “There are simple reflective exercises that this brain has limited capacity to accomplish.”

The DSM uses a categorical classification for diagnosis of depression, and Dr. Eist said he does not necessarily agree with the DSM-IV criteria. “Most clinicians add a dimensional element,” he said.

For example, in a dimensional classification, symptom intensity would also be taken into consideration in making a diagnosis. Also, the DSM requirement that the symptoms continue for a 2-week period seems inappropriate for diagnosis of mood disorders in teenagers, since mood changes in this age group are normal.

“I would recommend avoiding the trap of an arbitrary time limit,” Dr. Eist said. “I have examined and treated thousands of adolescents over the years, and I do not remember one who has remained in a dark mood for 2 weeks–other than a few who were seriously suicidal and hopeless.”

Adolescents require more sleep than do adults, and insomnia can be a sign of a mood disorder in an adolescent. It is critical to take a careful sleep history with all patients, but particularly with adolescents, Dr. Eist said. The number of hours that the adolescent sleeps each night is less important for diagnosis of depression than the amount of time it takes to fall asleep. Inability to fall asleep within 30 minutes is a sign of depression.

Major depression in adolescents often goes undetected because the rapidly changing moods fool both the adolescent and family members into believing that the adolescent is just “being a teenager.” In other cases, negativism and pessimism may be hidden by perfectionism. A chronically dissatisfied youngster is seen as not measuring up to his own high standards, rather than as having depression.

When it comes to adolescents, an inability to fall asleep within 30 minutes is a sign of depression. DR. EIST

MENDOZA, ARGENTINA – When it comes to adolescents with depression, psychiatrists would do well to tailor treatment to the individual needs of each patient, Dr. Harold I. Eist said at the 6th World Congress on Depressive Disorders.

Adolescence is a turbulent period with enormous biologic, psychological, and social changes, said Dr. Eist, a psychiatrist in private practice in Bethesda, Md., and a past president of the American Psychiatric Association. The brain of the adolescent is immature–“an impulsive, aggressive, thrill-seeking brain,” he said. “There are simple reflective exercises that this brain has limited capacity to accomplish.”

The DSM uses a categorical classification for diagnosis of depression, and Dr. Eist said he does not necessarily agree with the DSM-IV criteria. “Most clinicians add a dimensional element,” he said.

For example, in a dimensional classification, symptom intensity would also be taken into consideration in making a diagnosis. Also, the DSM requirement that the symptoms continue for a 2-week period seems inappropriate for diagnosis of mood disorders in teenagers, since mood changes in this age group are normal.

“I would recommend avoiding the trap of an arbitrary time limit,” Dr. Eist said. “I have examined and treated thousands of adolescents over the years, and I do not remember one who has remained in a dark mood for 2 weeks–other than a few who were seriously suicidal and hopeless.”

Adolescents require more sleep than do adults, and insomnia can be a sign of a mood disorder in an adolescent. It is critical to take a careful sleep history with all patients, but particularly with adolescents, Dr. Eist said. The number of hours that the adolescent sleeps each night is less important for diagnosis of depression than the amount of time it takes to fall asleep. Inability to fall asleep within 30 minutes is a sign of depression.

Major depression in adolescents often goes undetected because the rapidly changing moods fool both the adolescent and family members into believing that the adolescent is just “being a teenager.” In other cases, negativism and pessimism may be hidden by perfectionism. A chronically dissatisfied youngster is seen as not measuring up to his own high standards, rather than as having depression.

When it comes to adolescents, an inability to fall asleep within 30 minutes is a sign of depression. DR. EIST

MENDOZA, ARGENTINA – When it comes to adolescents with depression, psychiatrists would do well to tailor treatment to the individual needs of each patient, Dr. Harold I. Eist said at the 6th World Congress on Depressive Disorders.

Adolescence is a turbulent period with enormous biologic, psychological, and social changes, said Dr. Eist, a psychiatrist in private practice in Bethesda, Md., and a past president of the American Psychiatric Association. The brain of the adolescent is immature–“an impulsive, aggressive, thrill-seeking brain,” he said. “There are simple reflective exercises that this brain has limited capacity to accomplish.”

The DSM uses a categorical classification for diagnosis of depression, and Dr. Eist said he does not necessarily agree with the DSM-IV criteria. “Most clinicians add a dimensional element,” he said.

For example, in a dimensional classification, symptom intensity would also be taken into consideration in making a diagnosis. Also, the DSM requirement that the symptoms continue for a 2-week period seems inappropriate for diagnosis of mood disorders in teenagers, since mood changes in this age group are normal.

“I would recommend avoiding the trap of an arbitrary time limit,” Dr. Eist said. “I have examined and treated thousands of adolescents over the years, and I do not remember one who has remained in a dark mood for 2 weeks–other than a few who were seriously suicidal and hopeless.”

Adolescents require more sleep than do adults, and insomnia can be a sign of a mood disorder in an adolescent. It is critical to take a careful sleep history with all patients, but particularly with adolescents, Dr. Eist said. The number of hours that the adolescent sleeps each night is less important for diagnosis of depression than the amount of time it takes to fall asleep. Inability to fall asleep within 30 minutes is a sign of depression.

Major depression in adolescents often goes undetected because the rapidly changing moods fool both the adolescent and family members into believing that the adolescent is just “being a teenager.” In other cases, negativism and pessimism may be hidden by perfectionism. A chronically dissatisfied youngster is seen as not measuring up to his own high standards, rather than as having depression.

When it comes to adolescents, an inability to fall asleep within 30 minutes is a sign of depression. DR. EIST

Hemoglobin A_1c levels at hospital admission are predictive for hospital mortality and length of stay in diabetic patients with sepsis, reported Dr. Ivan Gornik of Rebro University Hospital in Zagreb, Croatia, and associates.

The investigators conducted a prospective, observational study of adults with type 2 diabetes admitted to a medical ward or medical intensive care unit because of sepsis. APACHE II and sequential organ failure assessment (SOFA) scores, plasma glucose levels, C-reactive protein (CRP), and leukocyte counts were determined upon hospital admission. HbA_1c levels were determined the following day.

The study was conducted from November 2003 to December 2005 and enrolled 286 adults, of which 121 (42%) were female. A total of 224 patients survived, with a median length of stay of 9 days (range 7–13). Of the 62 patients (22%) who died in the hospital, 32 (52%) were female.

Survivors were significantly younger than nonsurvivors were and had better APACHE II and SOFA scores. Median ages of survivors and nonsurvivors were 61 years (range 38–72) and 66 years (range 48–76), respectively (Diab. Res. Clin. Pract. 2006 [Epub doi:10.1016/j.diabres.2006.10.017]).

Survivors had significantly lower HbA_1c values (median 8.2%) than did nonsurvivors (median 9.75%).

In multivariate logistic regression analysis, HbA_1c level was an independent predictor of hospital mortality, with an adjusted odds ratio of 1.358 for each increase of 1%. In the same analysis, female gender, APACHE II score, and SOFA score were also independent predictors of hospital mortality, whereas age, plasma glucose levels at admission, and CRP were not.

Receiver operating curves analysis showed HbA_1c levels in survivors to be significantly correlated with length of hospital stay. HbA_1c scores did not correlate with plasma glucose levels, CRP, leukocyte count, age, APACHE II scores, or SOFA scores.

All patients with type 2 diabetes and sepsis should have strict glucose control, advised Dr. Gornik.

There is no additional treatment that can be offered to the subset of those patients with diabetes and sepsis who have high HbA_1c levels, but awareness of their condition might facilitate earlier detection and treatment of complications, he said.

Hemoglobin A_1c levels at hospital admission are predictive for hospital mortality and length of stay in diabetic patients with sepsis, reported Dr. Ivan Gornik of Rebro University Hospital in Zagreb, Croatia, and associates.

The investigators conducted a prospective, observational study of adults with type 2 diabetes admitted to a medical ward or medical intensive care unit because of sepsis. APACHE II and sequential organ failure assessment (SOFA) scores, plasma glucose levels, C-reactive protein (CRP), and leukocyte counts were determined upon hospital admission. HbA_1c levels were determined the following day.

The study was conducted from November 2003 to December 2005 and enrolled 286 adults, of which 121 (42%) were female. A total of 224 patients survived, with a median length of stay of 9 days (range 7–13). Of the 62 patients (22%) who died in the hospital, 32 (52%) were female.

Survivors were significantly younger than nonsurvivors were and had better APACHE II and SOFA scores. Median ages of survivors and nonsurvivors were 61 years (range 38–72) and 66 years (range 48–76), respectively (Diab. Res. Clin. Pract. 2006 [Epub doi:10.1016/j.diabres.2006.10.017]).

Survivors had significantly lower HbA_1c values (median 8.2%) than did nonsurvivors (median 9.75%).

In multivariate logistic regression analysis, HbA_1c level was an independent predictor of hospital mortality, with an adjusted odds ratio of 1.358 for each increase of 1%. In the same analysis, female gender, APACHE II score, and SOFA score were also independent predictors of hospital mortality, whereas age, plasma glucose levels at admission, and CRP were not.

Receiver operating curves analysis showed HbA_1c levels in survivors to be significantly correlated with length of hospital stay. HbA_1c scores did not correlate with plasma glucose levels, CRP, leukocyte count, age, APACHE II scores, or SOFA scores.

All patients with type 2 diabetes and sepsis should have strict glucose control, advised Dr. Gornik.

There is no additional treatment that can be offered to the subset of those patients with diabetes and sepsis who have high HbA_1c levels, but awareness of their condition might facilitate earlier detection and treatment of complications, he said.

Hemoglobin A_1c levels at hospital admission are predictive for hospital mortality and length of stay in diabetic patients with sepsis, reported Dr. Ivan Gornik of Rebro University Hospital in Zagreb, Croatia, and associates.

The investigators conducted a prospective, observational study of adults with type 2 diabetes admitted to a medical ward or medical intensive care unit because of sepsis. APACHE II and sequential organ failure assessment (SOFA) scores, plasma glucose levels, C-reactive protein (CRP), and leukocyte counts were determined upon hospital admission. HbA_1c levels were determined the following day.

The study was conducted from November 2003 to December 2005 and enrolled 286 adults, of which 121 (42%) were female. A total of 224 patients survived, with a median length of stay of 9 days (range 7–13). Of the 62 patients (22%) who died in the hospital, 32 (52%) were female.

Survivors were significantly younger than nonsurvivors were and had better APACHE II and SOFA scores. Median ages of survivors and nonsurvivors were 61 years (range 38–72) and 66 years (range 48–76), respectively (Diab. Res. Clin. Pract. 2006 [Epub doi:10.1016/j.diabres.2006.10.017]).

Survivors had significantly lower HbA_1c values (median 8.2%) than did nonsurvivors (median 9.75%).

In multivariate logistic regression analysis, HbA_1c level was an independent predictor of hospital mortality, with an adjusted odds ratio of 1.358 for each increase of 1%. In the same analysis, female gender, APACHE II score, and SOFA score were also independent predictors of hospital mortality, whereas age, plasma glucose levels at admission, and CRP were not.

Receiver operating curves analysis showed HbA_1c levels in survivors to be significantly correlated with length of hospital stay. HbA_1c scores did not correlate with plasma glucose levels, CRP, leukocyte count, age, APACHE II scores, or SOFA scores.

All patients with type 2 diabetes and sepsis should have strict glucose control, advised Dr. Gornik.

There is no additional treatment that can be offered to the subset of those patients with diabetes and sepsis who have high HbA_1c levels, but awareness of their condition might facilitate earlier detection and treatment of complications, he said.