Maintenance rituximab in Veterans with follicular lymphoma.

Real-world practice patterns and clinical outcomes in patients with follicular lymphoma (FL), including the adoption of maintenance rituximab (MR) therapy in the United States (US), have been reported in few studies since the release of the National LymphoCare Study almost a decade ago. We analyzed data from the largest integrated healthcare system in the United States, the Veterans Health Administration (VHA), to identify rates of adoption and effectiveness of MR in FL patients after first-line (1L) treatment. We identified previously untreated patients with FL in the VHA between 2006 and 2014 who achieved at least stable disease after chemoimmunotherapy or immunotherapy. Among these patients, those who initiated MR within 238 days of 1L composed the MR group, whereas those who did not were classified as the non-MR group. We examined the effect of MR on progression-free survival (PFS) and overall survival (OS). A total of 676 patients met our inclusion criteria, of whom 300 received MR. MR was associated with significant PFS (hazard ratio [HR]=0.55, P < .001) and OS (HR = 0.53, P = .005) compared to the non-MR group, after adjusting by age, sex, ethnicity, geographic region, diagnosis period, stage, grade at diagnosis, hemoglobin, lactate dehydrogenase (LDH), Charlson comorbidity index (CCI), 1L treatment regimen, and response to 1L treatment. These results suggest that in FL patients who do not experience disease progression after 1L treatment in real-world settings, MR is associated with a significant improvement in both PFS and OS. Maintenance therapy should be considered in FL patients who successfully complete and respond to 1L therapy.

Economic burden related to chemotherapy-related adverse events in patients with metastatic breast cancer in an integrated health care system.

BACKGROUND: Breast cancer is treated with many different modalities, including chemotherapy that can be given as a single agent or in combination. Patients often experience adverse events from chemotherapy during the cycles of treatment which can lead to economic burden. OBJECTIVE: The objective of this study was to evaluate costs related to chemotherapy-related adverse events in patients with metastatic breast cancer (mBC) in an integrated health care delivery system. METHODS: Patients with mBC newly initiated on chemotherapy were identified and the first infusion was defined as the index date. Patients were ≥18 years old at time of index date, had at least 6 months of health plan membership and drug eligibility prior to their index date. The chemotherapy adverse events were identified after the index date and during first line of chemotherapy. Episodes of care (EOC) were created using healthcare visits. Chart review was conducted to establish whether the adverse events were related to chemotherapy. Costs were calculated for each visit, including medications related to the adverse events, and aggregated to calculate the total EOC cost. RESULTS: A total of 1,682 patients with mBC were identified after applying study criteria; 54% of these patients had one or more adverse events related to chemotherapy. After applying the EOC method, there were a total of 5,475 episodes (4,185 single episodes [76.4%] and 1,290 multiple episodes [23.6%]) related to chemotherapy-related adverse events. Within single episodes, hematological (1,387 EOC, 33.1%), musculoskeletal/pain related (1,070 EOC, 25.6%), and gastrointestinal (775 EOC, 18.5%) were the most frequent adverse events. Patients with adverse events related to single EOC with anemia and neutropenia had the highest total outpatient costs with 901 EOC ($81,991) and 187 EOC ($17,017); these patients also had highest total inpatient costs with 46 EOC ($542,798) and 16 EOC ($136,768). However, within multiple episodes, hematological (420 EOC, 32.6%), followed by infections/pyrexia (335 EOC, 25.9%) and gastrointestinal (278 EOC, 22.6%) were the most frequent adverse events. CONCLUSION: The economic burden related to chemotherapy adverse events in patients with mBC is substantial.

Clinical Impact of Chemotherapy-Related Adverse Events in Patients with Metastatic Breast Cancer in an Integrated Health Care System.

BACKGROUND: Stage IV breast cancer, also known as metastatic breast cancer (mBC), is not a curable condition. However, treatment can prolong life, delay the progression of the cancer, or improve quality of life. Currently, patients with mBC are often treated with chemotherapy. Patients often experience adverse events from chemotherapy during the treatment cycle, which leads to chemotherapy modifications such as dose delay, dose reduction, or discontinuation of chemotherapy. Previous studies have evaluated the rates of adverse events that occur from the use of chemotherapy; however, few studies have evaluated the clinical impact on the chemotherapy regimen once the adverse event occurs. This study evaluates the clinical impact on the chemotherapy regimen from chemotherapy-related adverse events in patients with mBC in an integrated health care delivery system.   OBJECTIVES: To assess the adverse events in patients with mBC and evaluate the clinical impact on the chemotherapy regimen from these adverse events in an integrated health care delivery system.  METHODS: This study is a retrospective cohort of patients with mBC newly initiated on chemotherapy. The first infusion was defined as the index date. Patients were aged greater than 18 years at time of index date and had 6 months or more of Kaiser membership and drug eligibility prior to the index date and continuous membership and drug eligibility throughout follow-up. Adverse events were identified after the index date and during the follow-up using ICD-9-CM diagnosis and procedure codes. Single or multiple episodes of care were created from the adverse events. Chart review was conducted to establish whether the adverse event was related to chemotherapy and if any modification to the chemotherapy regimen occurred-a dose delay, dose reduction, or discontinuation was considered a clinical impact on therapy. Multivariate logistic regression was used to examine factors associated with clinical impact versus no clinical impact from the delivery of chemotherapy treatment.  RESULTS: A total of 1,682 patients with mBC were identified during our time period with an average follow-up of 2.21 years on first-line chemotherapy (SD = 1.83). 909 patients (54%) had at least 1 adverse event, and 773 patients (46%) did not have any adverse events during follow-up. Significant differences at baseline between these 2 groups included race, peripheral vascular disease, and length of stay (P less than 0.05). From the 909 patients who had at least 1 adverse event, 185 patients (20%) experienced an impact on their chemotherapy regimens. Patients with single episodes of care with any chemotherapy regimen impact experienced mostly hematological, infection/pyrexia, and gastrointestinal-related adverse events. In multiple episodes of care, neurological impact was more frequent than gastrointestinal-related effects. Patients with hospitalizations of greater than 3 days experienced the most impact, demonstrating that severe adverse events have more impact on chemotherapy regimens. In our multivariate analysis, patients aged greater than 65 years, having more than 1 comorbidity and having longer duration in days for each episode of care were all associated with clinical impact. Black and Hispanic patients were more likely to have a modification in their chemotherapy compared with white patients. CONCLUSIONS: This retrospective analysis demonstrates that chemotherapy-related adverse events in patients with mBC have an impact on the delivery of chemotherapy regimens. Having multiple comorbidities, increased age, and prolonged hospitalizations because of adverse events appear to be some of the primary factors related to chemotherapy modification.

Persistent recurring wheezing in the fifth year of life after laboratory-confirmed, medically attended respiratory syncytial virus infection in infancy.

BACKGROUND: Respiratory syncytial virus (RSV) infection in infancy is associated with subsequent recurrent wheezing. METHODS: A retrospective cohort study examined children born at ≥32 weeks gestation between 1996-2004. All children were enrolled in an integrated health care delivery system in Northern California and were followed through the fifth year of life. The primary endpoint was recurrent wheezing in the fifth year of life and its association with laboratory-confirmed, medically-attended RSV infection during the first year, prematurity, and supplemental oxygen during birth hospitalization. Other outcomes measured were recurrent wheezing quantified through outpatient visits, inpatient hospital stays, and asthma prescriptions. RESULTS: The study sample included 72,602 children. The rate of recurrent wheezing in the second year was 5.6% and fell to 4.7% by the fifth year. Recurrent wheezing rates varied by risk status: the rate was 12.5% among infants with RSV hospitalization, 8% among infants 32-33 weeks gestation, and 18% in infants with bronchopulmonary dysplasia. In multivariate analyses, increasing severity of respiratory syncytial virus infection was significantly associated with recurrent wheezing in year 5; compared with children without RSV infection in infancy, children who only had an outpatient RSV encounter had an adjusted odds ratio of 1.38 (95% CI,1.03-1.85), while children with a prolonged RSV hospitalization had an adjusted odds ratio of 2.59 (95% CI, 1.49-4.50). CONCLUSIONS: Laboratory-confirmed, medically attended RSV infection, prematurity, and neonatal exposure to supplemental oxygen have independent associations with development of recurrent wheezing in the fifth year of life.

Frequency, duration and predictors of bronchiolitis episodes of care among infants ≥32 weeks gestation in a large integrated healthcare system: a retrospective cohort study.

BACKGROUND: Bronchiolitis is common in the first two years of life and is the most frequent cause of hospitalization in this age group. No previous studies have used an episode-of-care analysis to describe the frequency, duration, and predictors of bronchiolitis episodes of care during the first two years. METHODS: We conducted a retrospective cohort study of 123,264 infants ≥32 weeks gestation born at 6 Northern California Kaiser Permanente hospitals between 1996 and 2002. We used electronic medical records to concatenate hospital, emergency department and outpatient health care encounters for bronchiolitis into discrete episodes of care. We used descriptive statistics to report frequency and duration of bronchiolitis episodes and used logistic regression to assess the effect of gestational age and other clinical and demographic predictors on the outcome of bronchiolitis episodes. RESULTS: Among all infants, the rate of bronchiolitis episodes was 162 per 1000 children during the first 2 years of life; approximately 40% required >1 day of medical attention with a mean duration of 7.0 ± 5.9 days. Prematurity was associated with increased risk of bronchiolitis episodes and longer duration. Bronchiolitis episodes rates per 1000 infants were 246 for 32-33 weeks gestational age, 204 for 34-36 weeks, and 148-178 for >36 weeks. Male gender, African-American and Hispanic race/ethnicity, and parental history of asthma were associated with an increased risk of having a bronchiolitis episode and/or longer duration. CONCLUSIONS: Bronchiolitis episodes of care are frequent during the first two years of life and the duration ranges from 1 to 27 days. Prematurity was associated with more frequent and longer duration of bronchiolitis episodes of care, which may reflect illness severity and/or perceived vulnerability.

Recurrent wheezing in the third year of life among children born at 32 weeks' gestation or later: relationship to laboratory-confirmed, medically attended infection with respiratory syncytial virus during the first year of life.

OBJECTIVE: To quantify the relationship between recurrent wheezing (RW) in the third year of life and respiratory syncytial virus (RSV) infection, prematurity, and neonatal oxygen exposure. DESIGN: Retrospective cohort study linking inpatient, outpatient, and laboratory databases for cohort assembly and logistic regression analysis. SETTING: Integrated health care delivery system in Northern California. PARTICIPANTS: A total of 71,102 children born from 1996 to 2002 at 32 weeks' gestational age or later who were health plan members for 9 or more months in their first and third years. MAIN EXPOSURES: Laboratory-confirmed, medically attended RSV infection during first year and supplemental oxygen during birth hospitalization. OUTCOME MEASURES: Recurrent wheezing, quantified through outpatient visits, inpatient hospital stays, and asthma prescriptions. RESULTS: The rate of RW in the third year of life was 16.23% among premature infants with RSV and 6.22% among those without RSV. The risk of RW increased among infants who had an RSV outpatient encounter (adjusted odds ratio [AOR], 2.07; 95% CI, 1.61-2.67), uncomplicated RSV hospitalization (AOR, 4.66; 95% CI, 3.55-6.12), or prolonged RSV hospitalization (AOR, 3.42; 95% CI, 2.01-5.82) compared with infants without RSV encounters. Gestational age of 34 to 36 weeks was associated with increased risk of RW (AOR, 1.23; 95% CI 1.07-1.41) compared with 38 to 40 weeks, while a gestational age of 41 weeks or more was protective (AOR, 0.90; 95% CI, 0.81-0.99). Supplemental oxygen exposure was associated with increased risk at all levels. CONCLUSION: Laboratory-confirmed, medically attended RSV infection, prematurity, and exposure to supplemental oxygen during the neonatal period have independent associations with the development of RW in the third year of life.

Respiratory syncytial virus testing during bronchiolitis episodes of care in an integrated health care delivery system: a retrospective cohort study.

BACKGROUND: Bronchiolitis has the highest incidence rate of any lower respiratory infection among infants and children <2 years of age. Respiratory syncytial virus (RSV) is the most common etiology of bronchiolitis. The American Academy of Pediatrics does not recommend routine RSV testing for infants and children with bronchiolitis. The clinical predictors of RSV testing are unknown. OBJECTIVES: The aims of this study were to identify the rates and predictors of RSV testing during bronchiolitis and to explore the relationship between RSV test results and antibiotic treatment among infants and children aged <2 years. METHODS: A retrospective study was conducted of 123,264 infants ≥32 weeks' gestational age (GA) who were born at 1 of 6 Northern California Kaiser Permanente Medical Center Program hospitals between 1996 and 2004. A bronchiolitis episode of care (EOC) was defined as ≥1 medical encounters with a bronchiolitis diagnosis code followed by 14 clear days without a bronchiolitis-related medical encounter. Descriptive statistics were used to report the frequency of tests, and logistic regression was used to assess the effect of hospitalization, chronologic age, gestational age, and season on the frequency of testing for RSV. Rapid direct fluorescent antibody testing was performed during the study. RESULTS: The birth cohort was 51.2% male and 42.7% white, 20.8% Hispanic, 20.3% Asian, 8.4% African American, and 7.9% other. Of 23,748 bronchiolitis EOCs, 4969 (20.9%) had ≥1 test for RSV. Overall, 44.2% of all tests were positive for RSV. Physicians ordered RSV tests in 30.4% and 26.7% of bronchiolitis EOCs for infants born at 32 to 33 and 34 to 36 weeks' GA, respectively, compared with 17.9% of bronchiolitis EOCs for infants born at ≥41 weeks' GA. Bronchiolitis hospitalization, younger chronologic age, prematurity, and RSV season were associated with RSV testing in a multivariate model controlling for other variables, with an adjusted odds ratio (AOR) of 28.55 (95% CI, 24.99-36.62) for hospitalization status; AOR of 6.89 (95% CI, 5.19-9.15) for chronologic age <1 month; AOR of 0.85 (95% CI, 0.76-0.95) for GA >41 weeks; and AOR of 2.48 (95% CI, 2.24-2.74) for RSV season (December-March). Among hospitalized infants who were tested and had a diagnostic code suggesting treatment with antibiotics, use of antibiotics was significantly lower among those with a positive RSV test (63.4%) than those with a negative RSV test (75.5%) (χ(2) test; P < 0.001). CONCLUSIONS: Approximately 20% of these children with bronchiolitis EOCs were tested for RSV; of those tested, about half were positive. In this integrated health care system, hospitalization with bronchiolitis, chronologic age, gestational age <37 weeks, neonatal oxygen exposure, and bronchiolitis EOC during the RSV season were the factors associated with testing for RSV.