Harmonized Outcome Measures for Use in Non-Small Cell Lung Cancer Patient Registries and Clinical Practice.

BACKGROUND: Lung cancer is the leading cause of cancer-related death in the United States and globally, and many questions exist about treatment options. Harmonizing data across registries and other data collection efforts would yield a robust data infrastructure to help address many research questions. The purpose of this project was to develop a minimum set of patient and clinician relevant harmonized outcome measures that can be collected in non-small cell lung cancer (NSCLC) patient registries and clinical practice. METHODS: Seventeen lung cancer registries and related efforts were identified and invited to submit outcome measures. Representatives from medical specialty societies, government agencies, health systems, health information technology groups, patient advocacy organizations, and industry formed a stakeholder panel to categorize the measures and harmonize definitions using the Agency for Healthcare Research and Quality's supported Outcome Measures Framework (OMF). RESULTS: The panel reviewed 66 outcome measures and identified a minimum set of 8 broadly relevant measures in the OMF categories of patient survival, clinical response, events of interest, and resource utilization. The panel harmonized definitions for the 8 measures through in-person and virtual meetings. The panel did not reach consensus on 1 specific validated instrument for capturing patient-reported outcomes. The minimum set of harmonized outcome measures is broadly relevant to clinicians and patients and feasible to capture across NSCLC disease stages and treatment pathways. A pilot test of these measures would be useful to document the burden and value of the measures for research and in clinical practice. CONCLUSIONS: By collecting the harmonized measures consistently, registries and other data collection systems could contribute to the development research infrastructure and learning health systems to support new research and improve patient outcomes.

A cross-sectional survey of work and income loss consideration among patients with herpes zoster when completing a quality of life questionnaire.

BACKGROUND: Prior research suggests that many patients do not spontaneously include work/income loss when responding to utility assessments, although this remains unconfirmed in the US due to almost no published US-based studies to date, and has not been previously studied among patients with herpes zoster (HZ). The objective of this study was to examine whether patients with HZ consider work and income loss when completing a quality of life survey. METHODS: A cross-sectional survey was administered to 2000 US adult commercial health plan enrollees aged 50-64 years with ≥ 1 HZ medical claim during 2014. The survey collected information related to health status (EQ-5D), work productivity, and HZ severity and clinical features. RESULTS: Mean respondent age was 58.4 years [standard deviation (SD) 4.1] and 62.0% were female. About 3 in 4 (76.8%) patients (N = 772) were employed either full (69.9%) or part time (6.9%). Less than half (45%) spontaneously considered work/income loss when responding to EQ-5D, and mean EQ-5D scores for patients who considered work/income loss were lower than for patients who did not [0.56 (SD = 0.28) vs. 0.69 (SD = 0.24); p < 0.001]. Overall, 43% of patients reported at least one full day missed (mean = 9 full days) and 29% reported at least one partial day missed (mean = 6 partial days) during the most recent shingles episode. Patients who considered work loss were more likely to have missed full (76.4% vs 26.0%, p < 0.001) or partial (70.9% vs. 35.2%, p < 0.001) days. Patients with absenteeism were more likely to consider work/income loss when completing EQ-5D [odds ratio (OR) = 7.91, 95% confidence interval (CI) 5.01-12.31]. Odds of absenteeism/presenteeism increased significantly with increasing levels of HZ severity, and higher odds were associated with pain located on the face/scalp/neck/eye/ear (OR 1.90, 95% CI 1.06-3.40) and with pain lasting 12+ months (OR = 2.91, 95% CI 1.14-7.42). CONCLUSIONS: HZ has considerable impact on the work and productivity of adults aged 50-64 years old. However, many patients with HZ do not spontaneously consider work/income loss when completing a standardized quality of life questionnaire. Studies that use health state utilities in HZ based on EQ-5D may not fully reflect the societal costs of work loss.

Characteristics and Outcome of AKT1 E17K-Mutant Breast Cancer Defined through AACR Project GENIE, a Clinicogenomic Registry.

AKT inhibitors have promising activity in AKT1 E17K-mutant estrogen receptor (ER)-positive metastatic breast cancer, but the natural history of this rare genomic subtype remains unknown. Utilizing AACR Project GENIE, an international clinicogenomic data-sharing consortium, we conducted a comparative analysis of clinical outcomes of patients with matched AKT1 E17K-mutant (n = 153) and AKT1-wild-type (n = 302) metastatic breast cancer. AKT1-mutant cases had similar adjusted overall survival (OS) compared with AKT1-wild-type controls (median OS, 24.1 vs. 29.9, respectively; P = 0.98). AKT1-mutant cases enjoyed longer durations on mTOR inhibitor therapy, an observation previously unrecognized in pivotal clinical trials due to the rarity of this alteration. Other baseline clinicopathologic features, as well as durations on other classes of therapy, were broadly similar. In summary, we demonstrate the feasibility of using a novel and publicly accessible clincogenomic registry to define outcomes in a rare genomically defined cancer subtype, an approach with broad applicability to precision oncology. SIGNIFICANCE: We delineate the natural history of a rare genomically distinct cancer, AKT1 E17K-mutant ER-positive breast cancer, using a publicly accessible registry of real-world patient data, thereby illustrating the potential to inform drug registration through synthetic control data.See related commentary by Castellanos and Baxi, p. 490.

Macrolide therapy and outcomes in a multicenter cohort of children hospitalized with Mycoplasma pneumoniae pneumonia.

BACKGROUND: Mycoplasma pneumoniae is a common cause of community-acquired pneumonia in childhood. Few studies have addressed the association of antimicrobial treatment and outcomes. OBJECTIVE: To determine whether macrolide therapy is associated with improved outcomes among children hospitalized with M. pneumoniae pneumonia. DESIGN: Multicenter retrospective cohort study. SETTING: Thirty-six children's hospitals which contribute data to the Pediatric Health Information System. PATIENTS: Children 6-18 years of age discharged with a diagnosis of M. pneumoniae pneumonia. MAIN EXPOSURE: Initial macrolide therapy. MAIN OUTCOME MEASURES: Length of stay (LOS), all-cause readmissions, and asthma-related hospitalizations. RESULTS: Empiric macrolide therapy was administered to 405 (58.7%) of 690 patients. The median LOS was 3 days (interquartile range, 2-6 days). Eight (1.2 %) patients were readmitted within 28 days, and 160 (23.2%) were readmitted within 15 months of index discharge. Ninety-five (13.7%) patients were hospitalized for asthma within 15 months of index discharge. Empiric macrolide therapy was associated with a 32% shorter overall LOS (adjusted beta-coefficient, -0.38; 95% confidence interval [CI]: -0.59 to -0.17). Macrolide therapy was not associated with all-cause readmission at 28 days (adjusted odds ratio, 1.12; 95% CI: 0.22-5.78) or 15 months (adjusted odds ratio, 1.00; 95% CI: 0.59-1.70) or with asthma-related hospitalizations at 15 months (adjusted odds ratio, 0.85; 95% CI: 0.36-1.97). CONCLUSION: In this large multicenter study of children hospitalized with M. pneumoniae pneumonia, empiric macrolide therapy was associated with a shorter hospital LOS. Macrolide therapy was not associated with 28-day or 15-month hospital readmission.

Health insurance and length of stay for children hospitalized with community-acquired pneumonia.

BACKGROUND: Disparities in patterns of care and outcomes for ambulatory-care sensitive childhood conditions such as community-acquired pneumonia (CAP) persist. However, the influence of insurance status on length of stay (LOS) for children hospitalized with CAP remains unexplored. METHODS: Secondary analysis of children (<18 years) hospitalized with CAP sampled in the Kids' Inpatient Database (KID) for years 1997, 2000, 2003, and 2006. Insurance status (private, public, uninsured) was based on claims data. Hospital LOS was calculated in days. Taking into account the complex sampling design, negative binomial regression models produced adjusted estimates of incidence rate ratios (IRR) for hospital LOS for children by insurance status. RESULTS: There was little variation in the categories of insurance status of children hospitalized with CAP between 1997 and 2006, with at least 40% privately insured, at least 40% publicly insured, and at least 5% uninsured in each sampled year. In all years, publicly insured children had a significantly longer hospital stay than privately insured children, and uninsured children had a significantly shorter hospital stay than privately insured children. These observed differences persisted after multivariate adjustment. CONCLUSIONS: Differences in LOS between uninsured, publicly insured, and privately insured children with CAP raise concerns about potential differences in hospital discharge practices related to insurance status and type. As healthcare reform is implemented, policy makers should strengthen efforts to reduce these disparities in order to achieve health for the population.

Influence of antibiotic susceptibility patterns on empiric antibiotic prescribing for children hospitalized with community-acquired pneumonia.

OBJECTIVE: The aim of this study was to determine the influence of pneumococcal penicillin-nonsusceptibility patterns on individual antibiotic prescription among 33 children's hospitals using a multilevel, random- intercept, logistic regression analysis. METHODS: It was a multilevel cross-sectional study. The participants were children, 1-18 years of age, with community-acquired pneumonia (CAP) who were discharged in 2006. Hospital antibiotic susceptibility data were collected from surveys, and patient data were obtained from an administrative database. The primary exposure was the proportion of penicillin-nonsusceptible pneumococcal isolates reported in 2005 by each hospital. A secondary exposure included using the proportion of penicillin-resistant pneumococcal isolates to determine whether a threshold of susceptibility existed. Receipt of broad-spectrum empiric antibiotic therapy in 2006 (ie, antibiotics other than penicillins or aminopenicillins) was the main outcome measure. RESULTS: Four thousand eight hundred eighty-eight children diagnosed with CAP were eligible. The proportion of penicillin-nonsusceptible isolates ranged from 9% to 70% across hospitals whereas the proportion of penicillin-resistant isolates ranged from 0% to 60%. Broad-spectrum antibiotics were prescribed to 93% of patients; 45% of patients received cephalosporin class antibiotics alone. There was no significant association between the proportion of pencillin-nonsusceptible pneumococcal isolates at individual hospitals and narrow-spectrum prescribing. However, every 10% increase in penicillin-resistant pneumococcal isolates was associated with a 39% increase in broad-spectrum antibiotic prescribing (adjusted odds ratio: 1.39; 95% confidence interval: 1.08-1.69). CONCLUSIONS: There was substantial variability in empiric antibiotic prescribing for CAP among children's hospitals in the United States. High-levels (ie, resistant) but not modest-levels (ie, intermediate susceptibility) of penicillin resistance were associated with broad-spectrum antibiotic prescribing.

Broad-range bacterial polymerase chain reaction in the microbiologic diagnosis of complicated pneumonia.

BACKGROUND: A bacterial cause is not frequently identified in children with pneumonia complicated by parapneumonic effusion (ie, complicated pneumonia). OBJECTIVES: To determine the frequency of positive blood and pleural fluid cultures in children with complicated pneumonia and to determine whether broad-range 16S rRNA polymerase chain reaction (PCR) improves identification of a microbiologic cause. METHODS: This prospective cohort study included children 1-18 years of age hospitalized with complicated pneumonia. RESULTS: Pleural fluid drainage was performed in 64 (51.6%) of 124 children with complicated pneumonia. A microbiologic cause was identified in 11 of 64 patients (17.2%; 95% confidence interval [CI]: 8.9%-28.7%). Bacteria were isolated from pleural fluid culture in 6 of 64 patients (9.4 %; 95% CI: 3.5%-19.3%) undergoing pleural drainage; the causative bacteria were Staphylococcus aureus (n = 5) and Streptococcus pneumoniae (n = 1). Blood culture identified a bacterial cause in 3 of 44 cases (6.8%; 95% CI: 1.4%-18.7%) undergoing pleural fluid drainage; S. pneumoniae (n = 1), Haemophilus influenzae (n = 1), and S. aureus (n = 1) were isolated. Only 3 of the 19 pleural fluid samples (15.8%; 95% CI: 3.4%-39.6%) analyzed with 16S rRNA PCR were positive. S. pneumoniae was the only organism detected in all three samples; two of these three had negative pleural fluid cultures and absence of bacteria on Gram stain. S. aureus was isolated from pleural fluid culture in one patient with a negative 16S rRNA PCR test. CONCLUSIONS: Causative bacteria were infrequently identified in children with complicated pneumonia. Broad-range 16S rRNA PCR only modestly improved the microbiologic yield over conventional culture methods.

Adjunct corticosteroids in children hospitalized with community-acquired pneumonia.

OBJECTIVE: To determine if systemic corticosteroid therapy is associated with improved outcomes for children hospitalized with community-acquired pneumonia (CAP). METHODS: In this multicenter, retrospective cohort study we used data from 36 children's hospitals for children aged 1 to 18 years with CAP. Main outcome measures were length of stay (LOS), readmission, and total hospitalization cost. The primary exposure was the use of adjunct systemic corticosteroids. Multivariable regression models and propensity scores were used to adjust for confounders. RESULTS: The 20 703 patients whose data were included had a median age of 4 years. Adjunct corticosteroid therapy was administered to 7234 patients (35%). The median LOS was 3 days, and 245 patients (1.2%) required readmission. Systemic corticosteroid therapy was associated with shorter LOS overall (adjusted hazard ratio [HR]: 1.24 [95% confidence interval (CI): 1.18-1.30]). Among children who received treatment with ß-agonists, the LOS was shorter for children who had received corticosteroids compared with children who had not (adjusted HR: 1.36 [95% CI: 1.28-1.45]). Among children who did not receive ß-agonists, the LOS was longer for those who received corticosteroids compared with those who did not (adjusted HR: 0.85 [95% CI: 0.75-0.96]). Corticosteroids were associated with readmission of patients who did not receive concomitant ß-agonist therapy (adjusted odds ratio: 1.97 [95% CI: 1.09-3.57]). CONCLUSIONS: For children hospitalized with CAP, adjunct corticosteroids were associated with a shorter hospital LOS among patients who received concomitant ß-agonist therapy. Among patients who did not receive this therapy, systemic corticosteroids were associated with a longer LOS and a greater odds of readmission. If ß-agonist therapy is considered a proxy for wheezing, our findings suggest that among patients admitted to the hospital with a diagnosis of CAP, only those with acute wheezing benefit from adjunct systemic corticosteroid therapy.

National hospitalization trends for pediatric pneumonia and associated complications.

OBJECTIVE: To determine current rates of and trends in hospitalizations for community-acquired pneumonia (CAP) and CAP-associated complications among children. METHODS: We performed a cross-sectional, retrospective, cohort study by using the 1997, 2000, 2003, and 2006 Kids' Inpatient Database. National estimates for CAP and CAP-associated local and systemic complication rates were calculated for children < or =18 years of age. Patients with comorbid conditions or in-hospital birth status were excluded. Percentage changes were calculated by using 1997 (before heptavalent pneumococcal conjugate vaccine [PCV7]) and 2006 (after PCV7) data. RESULTS: There were a total of 619,102 CAP discharges for 1997, 2000, 2003, and 2006, after application of inclusion and exclusion criteria. Overall rates of CAP discharges did not change substantially between 1997 and 2006, but stratification according to age revealed a 22% decrease for children <1 year of age, minimal change for children 1 to 5 years of age, and increases for children 6 to 12 years (22%) and > or =13 years (41%) of age. Systemic complication rates were highest among children <1 year of age but decreased by 36%. In all other age groups, systemic complication rates remained stable. Local complication rates increased 78% overall. Children 1 to 5 years of age had the highest local complication rates. CONCLUSIONS: After the introduction of PCV7 in 2000, rates of CAP-associated systemic complications decreased only for children <1 year of age. Rates of pediatric CAP-associated local complications are increasing in all age groups.

Vitamin E intake, alpha-tocopherol status, and pancreatic cancer in a cohort of male smokers.

BACKGROUND: Evidence indicates that vitamin E has anticarcinogenic properties for gastrointestinal cancers; however, few studies have examined this with respect to exocrine pancreatic cancer. OBJECTIVE: The objective was to examine whether vitamin E intake and serum alpha-tocopherol concentrations were prospectively associated with exocrine pancreatic cancer. DESIGN: We conducted a cohort analysis of prediagnostic vitamin E intake (4 tocopherols, 4 tocotrienols), serum alpha-tocopherol concentrations, and pancreatic cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study of male Finnish smokers aged 50-69 y at baseline. During follow-up from 1985 to 2004 (maximum: 19.4 y; median: 16 y), 318 incident cases were diagnosed among cohort participants with complete serum samples (n = 29,092); 306 cases had complete dietary data (n = 27,111). Cox proportional hazards models adjusted for age, smoking history, history of diabetes mellitus, and/or serum cholesterol were used to calculate hazard ratios (HRs) and 95% CIs. RESULTS: Higher alpha-tocopherol concentrations were associated with lower pancreatic cancer risk (highest compared with lowest quintile, HR: 0.52; 95% CI: 0.34, 0.80; P for trend = 0.03; continuous HR: 0.91; 95% CI: 0.84, 0.99). Polyunsaturated fat, a putative prooxidant nutrient, modified the association such that the inverse alpha-tocopherol association was most pronounced in subjects with a high polyunsaturated fat intake (ie, >9.9 g/d; highest compared with lowest quintile, HR: 0.38; 95% CI: 0.20, 0.70; P for trend = 0.03; continuous HR: 0.86; 95% CI: 0.75, 0.97; P for interaction = 0.05 and 0.02, respectively). No associations were observed for dietary tocopherols and tocotrienols. CONCLUSION: Our results support the hypothesis that higher alpha-tocopherol concentrations may play a protective role in pancreatic carcinogenesis in male smokers.