Kevin J. Psoter

Predictors of non-referral of patients with cystic fibrosis for lung transplant evaluation in the United States☆

BACKGROUND Lung transplantation is an intervention that improves survival for adult patients with cystic fibrosis (CF). Some patients with CF are never referred for lung transplant evaluation despite meeting physiologic criteria for referral. METHODS We performed a retrospective analysis of adult patients (≥18years of age) in the Cystic Fibrosis Foundation Patient Registry (CFFPR), eligible for their first evaluation for lung transplantation during the years 2001-2008 based on FEV1<30% predicted in two consecutive years. RESULTS Within the CFFPR, 1240 patients met eligibility criteria. Eight hundred and nine (65.2%) were referred for lung transplant evaluation, and 431 (34.8%) were not referred. In a multivariable model, Medicaid insurance (OR 1.79, 95% CI 1.29-2.47), older age (per 5year increase; OR 1.25, 95% CI 1.13-1.39), lack of high school graduate education (OR 2.27, 95% CI 1.42-3.64), and Burkholderia cepacia complex sputum culture positivity (OR 2.48, 95% CI 1.50-4.12) were associated with non-referral, while number of pulmonary exacerbations (OR 0.93, 95% CI 0.87-0.99) and supplemental oxygen use (OR 0.59, 95% CI 0.43-0.81) were associated with increased referral. CONCLUSIONS Despite meeting lung function criteria for lung transplant evaluation, 35% of patients with CF had not yet been referred to a lung transplant center. Predictors of non-referral included markers of low socioeconomic status, older age and B. cepacia complex sputum culture. Further work is needed to understand the outcomes for non-referred patients in order to refine referral recommendations in this population.

Differential Geographical Risk of Initial Pseudomonas aeruginosa Acquisition in Young US Children With Cystic Fibrosis

Pseudomonas aeruginosa is the sentinel respiratory pathogen in cystic fibrosis patients. We conducted a retrospective study to examine whether state of residence affected risk of P. aeruginosa acquisition among US children under 6 years of age with cystic fibrosis by using data from the Cystic Fibrosis Foundation National Patient Registry, 2003-2009. The outcome was time to first isolation of P. aeruginosa from a respiratory culture. We used a Bayesian hierarchical Weibull regression model with interval-censored outcomes. Spatial random effects, included at the state level and modeled using an intrinsic conditional autoregressive prior, allowed estimation of the residual spatial correlation. The regression portion of the model was adjusted for demographic and disease characteristics potentially affecting P. aeruginosa acquisition. A total of 3,608 children met the inclusion criteria and were followed for an average of 2.1 (standard deviation, 1.6) years. P. aeruginosa was cultured in 1,714 (48%) subjects. There was a moderately elevated spatial residual relative risk. An estimated 95% credible interval for the residual hazard ratio under 1 of the fitted models was 0.64-1.57; the strongest positive association was observed in the Southern states. The fact that risk for P. aeruginosa acquisition displayed spatial dependence suggests that regional factors, such as climate, may play an important role in P. aeruginosa acquisition.

Association of meteorological and geographical factors and risk of initial Pseudomonas aeruginosa acquisition in young children with cystic fibrosis

Initial infection with the sentinel respiratory pathogen in children with cystic fibrosis (CF), Pseudomonas aeruginosa (Pa), is generally with environmental strains of this ubiquitous organism. The purpose of this study was to evaluate the associations between meteorological and geographical factors and risk of initial Pa acquisition in young children with CF. Using the U.S. Cystic Fibrosis Foundation Patient Registry from 2003 to 2009, 3463 patients met inclusion criteria, of which 48% (n = 1659) acquired Pa during follow-up. From multivariable Weibull regression, increased risk of Pa acquisition was associated with increasing temperature [hazard ratio (HR) per 1 °C: 1·13; 95% confidence interval (CI) 1·08-1·13], dew point (HR per 1 °C: 1·10, 95% CI 1·07-1·13), rainfall (HR per cm: 1·10, 95% CI 1·07-1·12), latitude (HR per 1 °C northing: 1·15, 95% CI 1·11-1·20), longitude (HR per 1 °C easting: 1·01, 95% CI 1·01-1·02) and elevation (HR per 100 m: 1·05, 95% CI 1·03-1·07). These results suggest that environmental factors may play a previously unrecognized role in the aetiology of initial Pa acquisition.

Seasonality of acquisition of respiratory bacterial pathogens in young children with cystic fibrosis

BackgroundSeasonal variations are often observed for respiratory tract infections; however, limited information is available regarding seasonal patterns of acquisition of common cystic fibrosis (CF)-related respiratory pathogens. We previously reported differential seasonal acquisition of Pseudomonas aeruginosa in young children with CF and no such variation for methicillin-susceptible Staphylococcus aureus acquisition. The purpose of this study was to describe and compare the seasonal incidence of acquisition of other respiratory bacterial pathogens in young children with CF.MethodsWe conducted a retrospective study to describe and compare the seasonal incidence of methicillin-resistant Staphylococcus aureus (MRSA), Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Haemophilus influenzae acquisition in young CF patients residing in the U.S. using the Cystic Fibrosis Foundation National Patient Registry, 2003-2009. Log-linear overdispersed Poisson regression was used to evaluate seasonal acquisition of each of these pathogens.ResultsA total of 4552 children met inclusion criteria. During follow-up 910 (20%), 1161 (26%), 228 (5%), and 2148 (47%) children acquired MRSA, S. maltophilia, A. xylosoxidans and H. influenzae, respectively. Compared to winter season, MRSA was less frequently acquired in spring (Incidence Rate Ratio [IRR]: 0.79; 95% Confidence Interval [CI]: 0.65, 0.96) and summer (IRR: 0.69; 95% CI: 0.57, 0.84) seasons. Similarly, a lower rate of A. xylosoxidans acquisition was observed in spring (IRR: 0.59; 95% CI: 0.39, 0.89). For H. influenzae, summer (IRR: 0.88; 95% CI: 0.78, 0.99) and autumn (IRR: 0.78; 95% CI: 0.69, 0.88) seasons were associated with lower acquisition rates compared to winter. No seasonal variation was observed for S. maltophilia acquisition.ConclusionAcquisition of CF-related respiratory pathogens displays seasonal variation in young children with CF, with the highest rate of acquisition for most pathogens occurring in the winter. Investigation of factors underlying these observed associations may contribute to our understanding of the aetiology of these infections and guide future infection control strategies.

Risk factors for persistent Aspergillus respiratory isolation in cystic fibrosis

BACKGROUND Aspergillus species are increasingly detected in the respiratory tracts of individuals with cystic fibrosis (CF), and chronic Aspergillus fumigatus is associated with more frequent hospitalizations for pulmonary exacerbations. However, patient and clinical factors that may contribute to the acquisition of persistent Aspergillus infection have yet to be identified. The objective of this study was to identify risk factors for development of Aspergillus respiratory isolation in CF. METHODS A retrospective cohort study of participants in the CF Foundation Patient Registry between 2006 and 2012 was conducted. Generalized estimating equation models were used to evaluate the association between the development of persistent Aspergillus respiratory isolation and individual level demographic and clinical characteristics. RESULTS Among 16,095 individuals with CF followed from 2006 to 2012, 1541 (9.6%) subjects developed persistent Aspergillus isolation. White race (Odds Ratio [OR] 1.74, 95% confidence interval 1.23, 2.48, p<0.001) and pancreatic insufficiency (OR 1.50, 95% CI 1.09, 2.06, p<0.001) were found to be risk factors for persistent Aspergillus isolation. Chronic therapies, including inhaled antibiotics (OR 1.33; 95% CI 1.21, 1.46), macrolides (OR 1.23, 95% CI 1.14, 1.32, p<0.001), and inhaled corticosteroids (OR 1.13, 95% CI 1.04, 1.20, p<0.001) were also independently associated with an increased risk for persistent Aspergillus isolation. CONCLUSIONS We identified macrolides and inhaled antibiotics, which individually have been shown to improve CF outcomes, and inhaled corticosteroids as risk factors for developing persistent Aspergillus isolation. Further work is needed to determine whether these associations are causal or due to confounding by other factors.

Outpatient parenteral therapy for complicated Staphylococcus aureus infections: a snapshot of processes and outcomes in the real world

Abstract Background In the United States, patients discharged on outpatient parenteral antimicrobial therapy (OPAT) are often treated by home health companies (HHCs) or skilled nursing facilities (SNFs). Little is known about differences in processes and outcomes between these sites of care. Methods We performed a retrospective study of 107 patients with complicated Staphylococcus aureus infections discharged on OPAT from 2 academic medical centers. Clinical characteristics, site of posthospital care, process measures (lab test monitoring, clinic follow-up), adverse events (adverse drug events, Clostridium difficile infection, line events), and clinical outcomes at 90 days (cure, relapse, hospital readmission) were collected. Comparisons between HHCs and SNFs were conducted. Results Overall, 33% of patients experienced an adverse event during OPAT, and 64% were readmitted at 90 days. Labs were received for 44% of patients in SNFs and 56% of patients in HHCs. At 90 days after discharge, a higher proportion of patients discharged to an SNF were lost to follow-up (17% vs 3%; P = .03) and had line-related adverse events (18% vs 2%; P < .01). Patients discharged to both sites of care experienced similar clinical outcomes, with favorable outcomes occurring in 61% of SNF patients and 70% of HHC patients at 90 days. There were no differences in rates of relapse, readmission, or mortality. Conclusions Patients discharged to SNFs may be at higher risk for line events than patients discharged to HHCs. Efforts should be made to strengthen basic OPAT processes, such as lab monitoring and clinic follow-up, at both sites of care.

Tumor Site and Breast Cancer Prognosis

Introduction Various factors affect breast cancer prognosis; however, little information is available regarding the role of primary tumor site. The purpose of this study was to compare the survival and clinicopathologic characteristics of patients with breast cancer by primary tumor location. Materials and Methods We analyzed a prospectively collected single‐institution breast cancer registry. Univariate and multivariable analyses were used to evaluate the association of tumor site with positive lymph node status, presence of metastasis, time to recurrence or death, and events of recurrence or death. Patients with tumors originating from the upper‐outer quadrant were the reference group. Results From 2003 to 2015, 5295 patients with breast cancer were identified. Tumors originated from the upper‐outer quadrant (36.2%), upper‐inner quadrant (13.1%), lower‐outer quadrant (9.8%), lower‐inner quadrant (7.6%), nipple (1.2%), axillary tail (0.3%), or overlapping (24.7%). Tumors originated from overlapping lesions (odds ratio [OR], 1.58; 95% confidence interval [CI], 1.36‐1.83) had higher odds of positive axillary lymph nodes, whereas tumors from the upper‐inner (OR, 0.68; 95% CI, 0.56‐0.84) and lower‐inner quadrant (OR, 0.72; 95% CI, 0.56‐0.93) had lower odds. Tumors from the lower‐outer quadrant were associated with lower risk of death (hazard ratio, 0.64; 95% CI, 0.46‐0.88), whereas tumors from overlapping lesions had higher risk (hazard ratio, 1.28; 95% CI, 1.05‐1.55). Conclusion The site of primary tumor may be an important characteristic affecting the prognosis of patients with breast cancer. Micro‐Abstract The present study is a retrospective review of a prospectively collected institutional cancer registry. We evaluated more than 5000 patients to explore the role of primary tumor location in breast cancer prognosis. Our results indicate that tumors of different primary tumor sites in the breast behave differently and survival differences should be expected.