Jonathan A. Finkelstein

Direct health care costs of Crohn's disease and ulcerative colitis in US children and adults.

BACKGROUND & AIMS Data regarding the health care costs of inflammatory bowel disease (IBD) in the United States are limited. The objectives of this study were to estimate the direct costs of Crohns disease (CD) and ulcerative colitis (UC) in the United States, describe the distribution of costs among inpatient, outpatient, and pharmaceutical services, and identify sociodemographic factors influencing these costs. METHODS We extracted medical and pharmacy claims from an administrative database containing insurance claims from 87 health plans in 33 states, occurring between 2003 and 2004. We identified cases of CD and UC using an administrative definition. For each case, we selected up to 3 non-IBD controls. Claims were classified as inpatient, outpatient, or pharmaceutical according to Current Procedural Terminology codes or National Drug Codes. Costs were based on the paid amount of each claim. IBD-attributable costs were estimated by subtracting costs for non-IBD patients from those for patients with IBD. Logistic regression was used to identify the sociodemographic factors affecting these costs. RESULTS We identified 9056 patients with CD and 10,364 patients with UC. Mean annual costs for CD and UC were

Emergence of 19A as virulent and multidrug resistant pneumococcus in Massachusetts following universal immunization of infants with pneumococcal conjugate vaccine

8265 and

Post-PCV7 Changes in Colonizing Pneumococcal Serotypes in 16 Massachusetts Communities, 2001 and 2004

5066, respectively. For CD, 31% of costs were attributable to hospitalization, 33% to outpatient care, and 35% to pharmaceutical claims. The corresponding distribution for UC was 38%, 35%, and 27%, respectively. Costs were significantly higher for children younger than 20 years compared with adults, but this did not vary substantially by sex or region. CONCLUSIONS This study demonstrates a substantial economic burden of IBD and can be used to inform health policy.

Continued Impact of Pneumococcal Conjugate Vaccine on Carriage in Young Children

Background: The long-term effects of selective pressure from conjugate pneumococcal vaccine on the serotype distribution and antimicrobial resistance of carriage and invasive isolates of Streptococcus pneumoniae are unknown. Early changes demonstrate a reduction in vaccine serotypes and an increase in nonvaccine serotypes (NVT) among both carriage and invasive isolates. Ongoing surveillance is necessary to identify emerging invasive serotypes and antimicrobial susceptibilities. Methods: Enhanced surveillance of invasive pneumococcal disease in Massachusetts began in October 2001 and remains ongoing. Isolates from children less than 5 are sent to the Massachusetts Department of Public Health and subsequently to the Maxwell Finland laboratory for serotyping and determination of antimicrobial susceptibility. Annual incidence rates for vaccine serotype and NVT disease are calculated using 2000 census data. Results: NVT caused 72%–91% of invasive pneumococcal disease annually in children less than 5 years of age between 2002 and 2005. Serotype 19A has emerged as the most frequent cause of IPD in Massachusetts. A multidrug-resistant clone (ceftriaxone, amoxicillin, azithromycin and trimethoprim-sulfamethoxazole) (MLST 320) was first identified in Massachusetts in 2005. Conclusions: Three years after the introduction of pneumococcal conjugate vaccine for universal administration to children less than 2 in Massachusetts, a significant increase in invasive disease due to serotype 19A was observed. Although MLST 199 remains the most frequent sequence type among invasive isolates (of 19A), a multidrug-resistant sequence type, not previously identified in Massachusetts, has become an important cause of invasive disease. Further surveillance of the changing ecology of S. pneumoniae is necessary as a 4-year time period is not sufficient to fully evaluate the impact of PCV of pneumococcal infections.

Prevalence of Inappropriate Antibiotic Prescriptions Among US Ambulatory Care Visits, 2010-2011

Objective. The introduction of heptavalent conjugate pneumococcal vaccine (PCV7) has raised concerns for replacement with nonvaccine serotypes in both invasive disease and asymptomatic carriage. Analysis of colonizing serotypes among healthy children in the community provides critical data on such changes. Methods. Nasopharyngeal specimens were obtained from children who were younger than 7 years during well-child or sick visits in primary care practices in 16 Massachusetts communities during 2001 and 2004. Susceptibility testing and serotyping were performed on isolated Streptococcus pneumoniae strains. Vaccination history with PCV7 was abstracted from the medical record. Results. Among colonizing pneumococcal isolates, PCV7 serotypes decreased from 36% to 14%, and non-PCV7 serotypes increased from 34% to 55%. Overall carriage did not change (26% to 23%); neither did carriage of potentially cross-reactive serotypes (30% to 31%). The most common non-PCV7 serotypes were serotypes 11, 15, and 29. There was a substantial increase in penicillin nonsusceptibility from 8% to 25% in non-PCV7 serotypes; 35% were highly resistant to penicillin. Penicillin nonsusceptibility increased from 45% to 56% among PCV7 serotypes while remaining stable among PCV7 potentially cross-reactive strains (51% vs 54%). Conclusions. Pneumococcal colonization has changed after the introduction of PCV7, both in serotype distribution and in patterns of antibiotic resistance. The frequency of nonvaccine strains has increased, and the proportion of nonvaccine isolates that are not susceptible to penicillin has tripled. This shift toward increased carriage of nonvaccine serotypes warrants vigilance for changes in the epidemiology of invasive pneumococcal disease.

Impact of inhaled antiinflammatory therapy on hospitalization and emergency department visits for children with asthma

OBJECTIVES: The goals were to assess serial changes in Streptococcus pneumoniae serotypes and antibiotic resistance in young children and to evaluate whether risk factors for carriage have been altered by heptavalent pneumococcal conjugate vaccine (PCV7). METHODS: Nasopharyngeal specimens and questionnaire/medical record data were obtained from children 3 months to <7 years of age in primary care practices in 16 Massachusetts communities during the winter seasons of 2000–2001 and 2003–2004 and in 8 communities in 2006–2007. Antimicrobial susceptibility testing and serotyping were performed with S pneumoniae isolates. RESULTS: We collected 678, 988, and 972 specimens during the sampling periods in 2000–2001, 2003–2004, and 2006–2007, respectively. Carriage of non-PCV7 serotypes increased from 15% to 19% and 29% (P < .001), with vaccine serotypes decreasing to 3% of carried serotypes in 2006–2007. The relative contribution of several non-PCV7 serotypes, including 19A, 35B, and 23A, increased across sampling periods. By 2007, commonly carried serotypes included 19A (16%), 6A (12%), 15B/C (11%), 35B (9%), and 11A (8%), and high-prevalence serotypes seemed to have greater proportions of penicillin nonsusceptibility. In multivariate models, common predictors of pneumococcal carriage, such as child care attendance, upper respiratory tract infection, and the presence of young siblings, persisted. CONCLUSIONS: The virtual disappearance of vaccine serotypes in S pneumoniae carriage has occurred in young children, with rapid replacement with penicillin-nonsusceptible nonvaccine serotypes, particularly 19A and 35B. Except for the age group at highest risk, previous predictors of carriage, such as child care attendance and the presence of young siblings, have not been changed by the vaccine.

Population genomics of post-vaccine changes in pneumococcal epidemiology.

IMPORTANCE The National Action Plan for Combating Antibiotic-Resistant Bacteria set a goal of reducing inappropriate outpatient antibiotic use by 50% by 2020, but the extent of inappropriate outpatient antibiotic use is unknown. OBJECTIVE To estimate the rates of outpatient oral antibiotic prescribing by age and diagnosis, and the estimated portions of antibiotic use that may be inappropriate in adults and children in the United States. DESIGN, SETTING, AND PARTICIPANTS Using the 2010-2011 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, annual numbers and population-adjusted rates with 95% confidence intervals of ambulatory visits with oral antibiotic prescriptions by age, region, and diagnosis in the United States were estimated. EXPOSURES Ambulatory care visits. MAIN OUTCOMES AND MEASURES Based on national guidelines and regional variation in prescribing, diagnosis-specific prevalence and rates of total and appropriate antibiotic prescriptions were determined. These rates were combined to calculate an estimate of the appropriate annual rate of antibiotic prescriptions per 1000 population. RESULTS Of the 184,032 sampled visits, 12.6% of visits (95% CI, 12.0%-13.3%) resulted in antibiotic prescriptions. Sinusitis was the single diagnosis associated with the most antibiotic prescriptions per 1000 population (56 antibiotic prescriptions [95% CI, 48-64]), followed by suppurative otitis media (47 antibiotic prescriptions [95% CI, 41-54]), and pharyngitis (43 antibiotic prescriptions [95% CI, 38-49]). Collectively, acute respiratory conditions per 1000 population led to 221 antibiotic prescriptions (95% CI, 198-245) annually, but only 111 antibiotic prescriptions were estimated to be appropriate for these conditions. Per 1000 population, among all conditions and ages combined in 2010-2011, an estimated 506 antibiotic prescriptions (95% CI, 458-554) were written annually, and, of these, 353 antibiotic prescriptions were estimated to be appropriate antibiotic prescriptions. CONCLUSIONS AND RELEVANCE In the United States in 2010-2011, there was an estimated annual antibiotic prescription rate per 1000 population of 506, but only an estimated 353 antibiotic prescriptions were likely appropriate, supporting the need for establishing a goal for outpatient antibiotic stewardship.

Healthcare utilization and cost of pneumococcal disease in the United States

Objective. Although the efficacy of inhaled antiinflammatory therapy in improving symptoms and lung function in childhood asthma has been shown in clinical trials, the effectiveness of these medications in real-world practice settings in reducing acute health care use has not been well-evaluated. This study examined the effect of inhaled antiinflammatory therapy on hospitalizations and emergency department (ED) visits by children for asthma. Design. Defined population cohort study over 1 year. Setting. Three managed care organizations (MCOs) in Seattle, Boston, and Chicago participating in the Pediatric Asthma Care–Patient Outcome Research and Treatment II trial. Participants. All 11 195 children, between 3 to 15 years old, with a diagnosis of asthma who were enrolled in the 3 MCOs between July 1996 and June 1997. Outcome Measures. We identified children with 1 or more asthma diagnoses using automated encounter data. Medication dispensings were identified from automated pharmacy data. Multivariate logistic regression analysis was used to calculate effects of inhaled antiinflammatory therapy on the adjusted relative risk (RR) for hospitalization and ED visits for asthma. Results. Over 12 months, 217 (1.9%) of children had an asthma hospitalization, and 757 (6.8%) had an ED visit. After adjustment for age, gender, MCO, and reliever dispensing, compared with children who did not receive controllers, the adjusted RRs for an ED visit were: children with any (≥1) dispensing of cromolyn, 0.4 (95% confidence interval [CI]: 0.3, 0.5); any inhaled corticosteroid (ICS), 0.5 (95% CI: 0.4, 0.6); any cromolyn or ICS combined (any controller), 0.4 (95% CI: 0.3, 0.5). For hospitalization, the adjusted RR for cromolyn was 0.6 (95% CI: 0.4, 0.9), for ICS 0.4 (95% CI: 0.3, 0.7), and for any controller 0.4 (95% CI: 0.3, 0.6). A significant protective effect for both events was seen among children with 1 to 5 and with >5 antiinflammatory dispensings. When the analysis was stratified by frequency of reliever dispensing, there was a significant protective effect for controllers on ED visits for children with 1 to 5 and with >5 reliever dispensings and on the risk of hospitalization for children with >5 reliever dispensings. Conclusions. Inhaled antiinflammatory therapy is associated with a significant protective effect on the risk for hospitalization and ED visits in children with asthma. Cromolyn and ICSs were associated with similar effects on risks.asthma drug therapy, inhaled antiinflammatory agents, health maintenance organizations, hospitalization, emergency department.

Diversity and Antibiotic Resistance among Nonvaccine Serotypes of Streptococcus pneumoniae Carriage Isolates in the Post-Heptavalent Conjugate Vaccine Era

Whole-genome sequencing of 616 asymptomatically carried Streptococcus pneumoniae isolates was used to study the impact of the 7-valent pneumococcal conjugate vaccine. Comparison of closely related isolates showed the role of transformation in facilitating capsule switching to non-vaccine serotypes and the emergence of drug resistance. However, such recombination was found to occur at significantly different rates across the species, and the evolution of the population was primarily driven by changes in the frequency of distinct genotypes extant before the introduction of the vaccine. These alterations resulted in little overall effect on accessory genome composition at the population level, contrasting with the decrease in pneumococcal disease rates after the vaccines introduction.

Misunderstanding of Asthma Controller Medications: Association with Nonadherence

BACKGROUND Streptococcus pneumoniae continues to cause a variety of common clinical syndromes, despite vaccination programs for both adults and children. The total U.S. burden of pneumococcal disease is unknown. METHODS We constructed a decision tree-based model to estimate U.S. healthcare utilization and costs of pneumococcal disease in 2004. Data were obtained from the 2004-2005 National (Hospital) Ambulatory Medical Care Surveys (outpatient visits, antibiotics) and the National Hospital Discharge Survey (hospitalization rates), and CDC surveillance data. Other assumptions regarding the incidence of each syndrome due to pneumococcus, expected health outcomes, and healthcare utilization were derived from literature and expert opinion. Healthcare and time costs used 2007 dollars. RESULTS We estimate that, in 2004, pneumococcal disease caused 4.0 million illness episodes, 22,000 deaths, 445,000 hospitalizations, 774,000 emergency department visits, 5.0 million outpatient visits, and 4.1 million outpatient antibiotic prescriptions. Direct medical costs totaled