Screening practices for nontuberculous mycobacteria at US cystic fibrosis centers.

BACKGROUND: Current guidelines recommend at least once yearly screening for nontuberculous mycobacteria (NTM) in Cystic Fibrosis (CF), however screening practices remain widely variable. This study evaluates current practices among United States CF centers with specific focus on clinical predictive factors for NTM screening. METHODS: The CF Patient Registry (CFFPR) was queried for CF patients ages 10 and older with NTM cultures completed between 2010-2014. Predictors for screening were assessed using univariate and multivariate logistic regression. Centers were evaluated by groups based on screening rates for analysis of clinical drivers of screening. RESULTS: From 2010-2014 a total of 22,739 patients were identified with 17,177 (75.5%) tested for NTM during this time. In the overall cohort, those who were tested for NTM had lower pulmonary function (70.7% vs 83.9%), higher annual average of visits with pulmonary exacerbations (1.0 vs 0.3), and higher rate of coinfection with Pseudomonas aeruginosa (PA) as well as Methicillin resistant Staphylococcus aureus (MRSA). Among CF centers, pulmonary function, exacerbations, and coinfections with PA and MRSA were predictive of NTM screening in the lower screening cohort while pulmonary function was not predictive of screening in the highest screening cohort. Those programs who screened at a higher rate were successful in identifying NTM in more CF patients. CONCLUSION: NTM screening practices vary widely among United States CF centers with many centers testing only on clinical changes. With higher rates of testing shown as successful in identifying more patients with NTM, routine screening should be emphasized in CF care going forward.

A new side of sarcoidosis: medication and hospitalization use in a privately insured patient population.

OBJECTIVE: This study describes patterns of medication prescriptions for sarcoidosis patients in a large commercially insured U.S. population, with specific focus on prescribing practices across medical specialties and their associated hospitalization risk. METHODS: Using the Marketscan Database we selected adult patients with a diagnosis of sarcoidosis by ICD-9 code during the 2012 calendar year. Differences in prescribing practices were evaluated between provider types. A multivariate model controlling for age, sex, and region assessed hospitalization risk associated with provider type, prednisone dose, and use of non-steroid sarcoidosis medications. RESULTS: Using the described criteria, 11,042 total patients were identified. A majority were female, mean age 49.3 years. Of these, 1,792 (16.2%) had one or more hospital admissions (mean 1.6, SD 1.3) with a mean length of stay of 8.1 days (SD 14.5). 25.5% of patients were prescribed prednisone with a 1 year mean cumulative dose of 250mg. Pulmonary/Rheumatology providers prescribed the highest cumulative prednisone dose (961 mg) and were more likely to prescribe methotrexate and monoclonal antibody medications. Sarcoidosis patients receiving a cumulative prednisone dose >500 mg had an increased risk for hospitalization (OR 2.512, 2.210-2.855), while those prescribed methotrexate and azathioprine had decreased risk (OR 0.633, 0.481-0.833 and 0.460, 0.315-0.671). Monoclonal antibody use was associated with increased OR for hospitalization at 1.359. CONCLUSION: Sarcoidosis patients treated by subspecialists were more likely to receive higher doses of prednisone and non-steroid sarcoidosis medications. Higher doses of prednisone and monoclonal antibody use were associated with higher hospitalization risk while methotrexate and azathioprine were associated with lower hospitalization risk.

Quality improvement initiative to reduce deep vein thrombosis associated with peripherally inserted central catheters in adults with cystic fibrosis.

RATIONALE: Peripherally inserted central catheters (PICCs) are common in the treatment of patients with cystic fibrosis (CF). Previous reports suggest that patients with CF are at increased risk for PICC-associated deep vein thrombosis (DVT). OBJECTIVES: We assessed potential risk factors for symptomatic PICC-associated DVT with subsequent implementation of a quality improvement (QI) initiative to reduce PICC-associated DVT in patients with CF. METHODS: This was a 5-year retrospective cohort study with subsequent 21-month prospective observation following implementation of a QI intervention in adults (aged 18 yr or older) with CF. All patients with a PICC inserted from July 2006 to March 2013 at our CF Foundation-accredited center were included. Symptomatic DVT was diagnosed by Doppler ultrasound. PICC insertions were analyzed, and nine risk factors for DVT were analyzed to formulate a QI initiative to reduce risk of PICC-associated DVT. The QI program focused on staff education and included modification to PICC order entry with a 4 French (F) single-lumen (SL) catheter as standard for all patients with CF. MEASUREMENTS AND MAIN RESULTS: A total of 369 PICCs were analyzed in 117 unique patients for a total of 5,437 PICC-days of placement. Symptomatic DVT was diagnosed in 28 (7.6%) of the 369 PICCs analyzed. Using regression analysis, the strongest predictors for DVT occurrence were warfarin use (odds ratio [OR] = 9.2, P = 0.006) and history of PICC-associated DVT (OR = 2.97, P = 0.08). Insertion of a 4F SL PICC resulted in zero symptomatic DVT. Zero episodes of DVT associated with 4F PICC insertion prevented use of PICC size in regression analysis. However, univariate analysis revealed that insertion of a 4F SL PICC instead of either 5F double lumen or 6F triple lumen was associated with a reduction in PICC-associated DVT (P = 0.001). After the QI intervention, 4F SL catheter insertion substantially increased to 65.8% of all PICCs inserted, whereas 6F triple-lumen catheter insertion declined to 6.8% of PICCs inserted. The QI initiative resulted in an absolute risk reduction in DVT per PICC placed of 6.1% (P = 0.055). CONCLUSIONS: To reduce risk of PICC-associated DVT in patients with CF, QI strategies should focus on insertion of smaller-diameter 4F PICCs and reduction in PICC use in high-risk patients when possible.

Treatment with connexin 46 siRNA suppresses the growth of human Y79 retinoblastoma cell xenografts in vivo.

Tumors with a hypoxic component, including human Y79 retinoblastoma cells, express a specific gap junction protein, Connexin 46 (Cx46), which is usually only found in naturally hypoxic tissues such as the differentiated lens. The aim of this study was to investigate if Cx46 downregulation would suppress Y79 tumor formation in vivo. Five-week old nude mice were subcutaneously implanted with human Y79 retinoblastoma cells and treated with intratumor siRNA injections of 30 µg Cx46 siRNA (n = 6), 30 µg non-silencing siRNA (n = 6), or no siRNA treatment (n = 6) every 2 days for a maximum of 10 treatments. Tumor volume (TV) was calculated from the recorded caliper measurements of length and width. Excised tumors were measured and weighed. Western blot analyses were performed to evaluate Cx46 and Cx43 expression in tumors which received Cx46 siRNA, non-silencing siRNA, or no siRNA treatment. Tumor histopathology was used to assess tumor features. Cx46 siRNA treated Y79 tumors had a reduced TV (287 mm(3) ± 77 mm(3)) when compared to the tumors of mice receiving the negative control siRNA (894 mm(3) ± 218 mm(3); P ≤ 0.03) or no siRNA (1068 mm(3) ± 192 mm(3); P ≤ 0.002). A 6-fold knockdown of Cx46 and a 3-fold rise in Cx43 protein expression was observed from western blots of tumors treated with Cx46 siRNA compared to mice treated with non-silencing siRNA. Knockdown of Cx46 with siRNA had an antitumor effect on human Y79 retinoblastoma tumors in the nude mouse model. The results suggest that anti-Cx46 therapy may be a potential target in the future treatment of retinoblastoma.