Edward F. Mitchel

THE EFFECT OF INFLUENZA ON HOSPITALIZATIONS, OUTPATIENT VISITS, AND COURSES OF ANTIBIOTICS IN CHILDREN

BACKGROUND Despite high annual rates of influenza in children, influenza vaccines are given to children infrequently. We measured the disease burden of influenza in a large cohort of healthy children in the Tennessee Medicaid program who were younger than 15 years of age. METHODS We determined the rates of hospitalization for acute cardiopulmonary conditions, outpatient visits, and courses of antibiotics over a period of 19 consecutive years. Using the differences in the rates of these events when influenzavirus was circulating and the rates from November through April when there was no influenza in the community, we calculated morbidity attributable to influenza. There was a total of 2,035,143 person-years of observation. RESULTS During periods when influenzavirus was circulating, the average number of hospitalizations for cardiopulmonary conditions in excess of the expected number was 104 per 10,000 children per year for children younger than 6 months of age, 50 per 10,000 per year for those 6 months to less than 12 months, 19 per 10,000 per year for those 1 year to less than 3 years, 9 per 10,000 per year for those 3 years to less than 5 years, and 4 per 10,000 per year for those 5 years to less than 15 years. For every 100 children, an annual average of 6 to 15 outpatient visits and 3 to 9 courses of antibiotics were attributable to influenza. In winter, 10 to 30 percent of the excess number of courses of antibiotics occurred during periods when influenzavirus was circulating. CONCLUSIONS Healthy children younger than one year of age are hospitalized for illness attributable to influenza at rates similar to those for adults at high risk for influenza. The rate of hospitalization decreases markedly with age. Influenza accounts for a substantial number of outpatient visits and courses of antibiotics in children of all ages.

Evidence of a Causal Role of Winter Virus Infection during Infancy in Early Childhood Asthma

RATIONALE Bronchiolitis during infancy is associated with an increased risk of childhood asthma. Whether winter viral infections cause asthma or are a manifestation of a predisposition to asthma development is unknown. OBJECTIVES To study the relationship of winter virus infection during infancy and the development of childhood asthma. METHODS We studied over 95,000 infants born between 1995 and 2000 and followed through 2005 who were enrolled in the Tennessee Medicaid program from birth through early childhood to determine whether infant birth in relationship to the winter virus peak alters the risk of developing early childhood asthma. MEASUREMENTS AND MAIN RESULTS Among 95,310 children studied during five winter virus seasons from birth through early childhood, the risk of developing asthma tracked with the timing of infant birth in relationship to the winter virus peak. Infant birth approximately 4 months before the winter virus peak carried the highest risk, with a 29% increase in odds of developing asthma compared with birth 12 months before the peak (adjusted odds ratio, 1.29; 95% confidence interval, 1.19-1.40). Infant age at the winter virus peak was comparable to or greater than other known risk factors for asthma. CONCLUSIONS Timing of birth in relationship to winter virus season confers a differential and definable risk of developing early childhood asthma, establishing winter virus seasonality as a causal factor in asthma development. Delay of exposure or prevention of winter viral infection during early infancy could prevent asthma.

Maternal morbidity and perinatal outcomes among pregnant women with respiratory hospitalizations during influenza season

OBJECTIVES A population-based assessment of maternal and perinatal morbidity related to respiratory illness during influenza season among pregnant women has not been published. The objectives of this investigation were to describe and quantify the impact of respiratory hospitalization during pregnancy on serious maternal and perinatal morbidity. STUDY DESIGN A matched cohort study using an administrative database of pregnant women enrolled in the Tennessee Medicaid population to determine pregnancy outcomes associated with respiratory hospitalizations during influenza season. Pregnant women aged 15 to 44 years with a respiratory hospitalization during influenza seasons 1985-1993 were matched by gestational age and presence of comorbidity with pregnant control subjects without a respiratory hospitalization. RESULTS During the eight influenza seasons studied, 293 women with singleton pregnancies had respiratory disease hospitalizations (5.1:1000). Women with asthma had high rates of such hospitalization (59.7:1000). Compared with matched controls, women with respiratory hospitalizations had similar modes of delivery, delivery length of stay, and episodes of preterm labor. The prevalence of prematurity and low birth weight among infants born to such women was likewise similar between the two groups. CONCLUSION In this population of pregnant women, those with asthma accounted for half of all respiratory-related hospitalizations during influenza seasons, with 6% of pregnant women with asthma requiring respiratory hospitalization during influenza season, (odds ratio 10.63, 95% CI, 8.18-13.83, compared with women without a medical comorbidity). We detected no significant increase in adverse perinatal outcomes associated with respiratory hospitalizations during influenza season.

Reduction of frequent otitis media and pressure-equalizing tube insertions in children after introduction of pneumococcal conjugate vaccine

OBJECTIVE. Streptococcus pneumoniae is an important cause of otitis media in children. In this study we estimated the effect of routine childhood immunization with heptavalent pneumococcal conjugate vaccine on frequent otitis media (3 episodes in 6 months or 4 episodes in 1 year) and pressure-equalizing tube insertions. PATIENTS AND METHODS. The study population included all children who were enrolled at birth in TennCare or selected upstate New York commercial insurance plans as of July 1998 and continuously followed until 5 years old, loss of health plan enrollment, study outcome, or end of the study. We compared the risk of developing frequent otitis media or having pressure-equalizing tube insertion for 4 birth cohorts (1998–1999, 1999–2000, 2000–2001, and 2001–2002) by using Cox regression analysis. We used data from the National Immunization Survey to estimate the heptavalent pneumococcal conjugate vaccine uptake for children in these 4 birth cohorts in Tennessee and New York. RESULTS. The proportion of children in Tennessee and New York who received at least 3 doses of heptavalent pneumococcal conjugate vaccine by 2 years of age increased from ≤1% for the 1998–1999 birth cohort to ∼75% for the 2000–2001 birth cohort. By age 2 years, 29% of Tennessee and New York children born in 2000–2001 had developed frequent otitis media, and 6% of each of these birth cohorts had pressure-equalizing tubes inserted. Comparing the 2000–2001 birth cohort to the 1998–1999 birth cohort, frequent otitis media declined by 17% and 28%, and pressure-equalizing tube insertions declined by 16% and 23% for Tennessee and New York children, respectively. For the 2000–2001 to the 2001–2002 birth cohort, frequent otitis media and pressure-equalizing tubes remained stable in New York but increased in Tennessee. CONCLUSIONS. After heptavalent pneumococcal conjugate vaccine introduction, children were less likely to develop frequent otitis media or have pressure-equalizing tube insertions.

Maternal asthma and maternal smoking are associated with increased risk of bronchiolitis during infancy.

OBJECTIVE. Our goal was to determine whether maternal asthma and maternal smoking during pregnancy are associated with the incidence and severity of clinically significant bronchiolitis in term, otherwise healthy infants without the confounding factors of small lung size or underlying cardiac or pulmonary disease. PATIENTS AND METHODS. We conducted a population-based retrospective cohort study of term, non–low birth weight infants enrolled in the Tennessee Medicaid Program from 1995 to 2003. The cohort of infants was followed through the first year of life to determine the incidence and severity of bronchiolitis as determined by health care visits and prolonged hospitalization. RESULTS. A total of 101245 infants were included. Overall, 20% of infants had ≥1 health care visit for bronchiolitis. Compared with infants with neither factor, the risk of bronchiolitis was increased in infants with maternal smoking only, maternal asthma only, or both. Infants with maternal asthma only or with both maternal smoking and asthma had the highest risks for emergency department visits and hospitalizations. Infants with a mother with asthma had the highest risk of a hospitalization >3 days, followed by infants with both maternal asthma and smoking, and maternal smoking only. CONCLUSIONS. Maternal asthma and maternal smoking during pregnancy are independently associated with the development of bronchiolitis in term, non–low birth weight infants without preexisting cardiac or pulmonary disease. The risk of bronchiolitis among infants with mothers who both have asthma and smoke during pregnancy is ∼50% greater than that of infants with neither risk factor. Efforts to decrease the illness associated with these 2 risk factors will lead to decreased morbidity from bronchiolitis, the leading cause of hospitalization for severe lower respiratory tract infections during infancy.

Assessment of Adherence to and Persistence on Disease-Modifying Antirheumatic Drugs (DMARDs) in Patients With Rheumatoid Arthritis

Objective:Biologic disease-modifying antirheumatic drugs (DMARDs) are efficacious for treating rheumatoid arthritis (RA). However, measurements of relative effectiveness, including treatment adherence and persistence, are lacking. We evaluated adherence and persistence during new episodes of use of traditional and biologic DMARDs. Methods:Using Tennessee Medicaid databases (1995–2004), we assembled a retrospective cohort of patients diagnosed with RA, and identified new episodes of use for 12 DMARD regimens. We evaluated persistence through survival analyses, and adherence within episodes through the medication possession ratio. A risk score was included in the analyses to account for measured confounders. Results:We identified 14,932 patients with RA; 6018 patients had 10,547 episodes of new use of DMARDs. Considering methotrexate as the reference and after adjustment for measured confounders, episodes of new use of sulfasalazine [adjusted hazard ratio (aHR) = 1.59; 95% confidence interval (CI) = 1.47–1.72] and infliximab alone (aHR = 1.37, 95% CI = 1.09–1.73) were more likely to be discontinued; and new episodes of etanercept (aHR = 0.82, 95% CI = 0.73–0.92) and methotrexate + adalimumab (aHR = 0.63, 95% CI = 0.48–0.84) were less likely to be discontinued. Compared with methotrexate, adherence was higher for leflunomide, infliximab, etanercept, and adalimumab and lower for sulfasalazine and all combined therapies. Conclusions:We developed an approach to assess persistence on and adherence to the most common DMARD therapies. In this large cohort, persistence and adherence to leflunomide and most biologic DMARD therapies were at least comparable to methotrexate. Adherence was lower for sulfasalazine and all combined therapies.

Increasing burden and risk factors for bronchiolitis-related medical visits in infants enrolled in a state health care insurance plan.

OBJECTIVES. The goals were to estimate the year-round burden of health care visits attributable to bronchiolitis and to identify risk factors for bronchiolitis in term healthy infants. METHODS. We conducted a population-based, retrospective cohort study of 103 670 term, non–low birth weight infants enrolled in Tennessee Medicaid in 1995–2003. We monitored infants through the first year of life. Risk factors for bronchiolitis during infancy and rates of inpatient, emergency department, and outpatient visits during the study period were calculated by using claims data. RESULTS. Over the 9 study years, rates of bronchiolitis visits were 238 outpatient visits per 1000 infant-years, 77 emergency department visits per 1000 infant-years, and 71 hospitalizations per 1000 infant-years. Average annual rates of bronchiolitis visits increased 41%, from 188 visits per 1000 infant-years to 265 visits per 1000 infant-years, from 1996–1997 to 2002–2003. Analysis of the linear trend in 500-g increments demonstrated a negative association between increasing birth weight and bronchiolitis diagnosis. There was a significant negative trend between maternal age and infant bronchiolitis diagnosis. Compared with infants of mothers 20 to 29 years of age, infants of mothers 15 to 19 years of age had a small increase in risk of having a bronchiolitis visit, whereas infants of older mothers (30–39 or 40–44 years of age) were less likely to have a visit. CONCLUSIONS. The disease burden of bronchiolitis is substantial, with increasing rates of all types of visits among term, otherwise-healthy infants enrolled in Tennessee Medicaid between 1995 and 2003. Protective factors in this cohort of term infants included higher birth weight and older maternal age.

Influenza– and Respiratory Syncytial Virus–Associated Morbidity and Mortality in the Nursing Home Population

Objectives: To estimate winter viral‐related morbidity and mortality in Tennessee nursing home residents during 4 consecutive years.

Underutilization of Controller and Rescue Medications Among Older Adults with Asthma Requiring Hospital Care

BACKGROUND: Asthma causes serious morbidity in older people, but pharmacologic therapy in older people with asthma has never been studied, at least in part because of the difficulty of defining asthma in this population.

Changing patterns of medication use in patients with rheumatoid arthritis in a Medicaid population

OBJECTIVE To examine changes in patterns of medication utilization in patients with RA. METHODS Data from Tennessee Medicaid (TennCare) databases (1995-2004) were used to identify adults with both a diagnosis of RA and at least one DMARD prescription each year. Annual age-specific utilization of DMARDs, glucocorticoids, NSAIDs and narcotics was measured on the last day of each year to determine the point prevalence of use of these agents. RESULTS Records from 23 342 patients with treated RA were analysed. Most patients were females (78%) and white (74%). The median age was 57 yrs (interquartile range: 48-65). The proportion of patients who had a current DMARD prescription on the index date increased from 62% in 1995 to 71% in 2004 (P < 0.001). MTX was the most commonly used DMARD. By the end of 2004, 22% of patients had a current prescription for a biologic, and etanercept represented 51% of all biologic therapies. During the study period, the overall utilization of glucocorticoids decreased from 46% to 38% (P < 0.001), whereas NSAID utilization increased from 33% to 38% (P < 0.001), and use of narcotics increased from 38% to 55% (P < 0.001). A secondary analysis that identified RA patients based on diagnosis codes alone, showed similar patterns, but lower DMARD utilization which increased from 33% to 52% overall and from 0% to 16% for biologics. CONCLUSIONS The utilization of DMARDs increased in TennCare patients with RA, and by 2004, use of biologics was substantial. Although glucocorticoid utilization decreased, use of both NSAIDs and narcotics increased.