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Data with some values below a limit of detection (LOD) can be analyzed using methods of survival analysis for left-censored data. The reverse Kaplan-Meier (KM) estimator provides an effective method for estimating the distribution function and thus population percentiles for such data. Although developed in the 1970s and strongly advocated since then, it remains rarely used, partly due to limited software availability.In this paper, the reverse KM estimator is described and is illustrated using serum dioxin data from the University of Michigan Dioxin Exposure Study (UMDES) and the National Health and Nutrition Examination Survey (NHANES). Percentile estimates for left-censored data using the reverse KM estimator are compared with replacing values below the LOD with the LOD/2 or LOD/ radical2.When some LODs are in the upper range of the complete values, and/or the percent censored is high, the different methods can yield quite different percentile estimates. The reverse KM estimator, which is the nonparametric maximum likelihood estimator, is the preferred method. Software options are discussed: The reverse KM can be calculated using software for the KM estimator. The JMP and SAS (SAS Institute, Cary, NC) and Minitab (Minitab, Inc, State College, PA), software packages calculate the reverse KM directly using their Turnbull estimator routines.The reverse KM estimator is recommended for estimation of the distribution function and population percentiles in preference to commonly used methods such as substituting LOD/2 or LOD/ radical2 for values below the LOD, assuming a known parametric distribution, or using imputation to replace the left-censored values.

Purpose In 2009, the World Health Organization published a conceptual outcome framework for evaluating upper extremity injury and disease, known as the Brief International Classification of Functioning, Disability, and Health (ICF) Core Set for Hand Conditions. The purpose of this study was to apply the ICF conceptual model to outcomes for distal radius fractures (DRFs) and determine the contribution of each ICF domain to patient satisfaction. Methods Patient-rated and objective functional outcome data were collected at 6 weeks, 3 months, and 6 months after surgery. We measured satisfaction using a subsection of the Michigan Hand Outcomes Questionnaire (MHQ) satisfaction score. Measured study variables were linked to their corresponding ICF domain (personal factors, environmental factors, activity and participation, and body function). We then used hierarchical regression to assess the contribution of each ICF domain to variation in overall patient satisfaction at each time point. Results We enrolled 53 patients with unilateral DRFs treated with the volar locking plating system. Regression analysis indicated that measured study variables explain 93% (6 weeks), 98% (3 months), and 97% (6 months) of variation in patient satisfaction. For all 3 study assessment dates, activity and participation variables (MHQ–Activities of Daily Living, MHQ–Work, and Jebsen-Taylor Score) contributed the most to variation in patient satisfaction, whereas personal and environmental factors had a considerably smaller role in predicting changes in patient satisfaction. Conclusions The results demonstrated that it is possible to reliably model the relative contributions of each ICF domain to patient satisfaction over time, and the findings are consistent with previous research (ie, that most outcome variation is due to physical or functional factors). These results are strong enough to support continued use and further research using the ICF model for upper extremity outcomes.

BACKGROUND The majority (59 to 86%) of hospital-acquired urinary tract infections (UTIs) are catheter-associated urinary tract infections (CAUTI). As of 2008, claims data are used to deny payment for hospital-acquired conditions such as CAUTI and to publicly report hospital performance.

Recombinant factor VIII Fc fusion protein (rFVIIIFc) is a long-acting coagulation factor approved for the treatment of hemophilia A. Here, the rFVIIIFc manufacturing process and results of studies evaluating product quality and the capacity of the process to remove potential impurities and viruses are described. This manufacturing process utilized readily transferable and scalable unit operations and employed multi-step purification and viral clearance processing, including a novel affinity chromatography adsorbent and a 15 nm pore size virus removal nanofilter. A cell line derived from human embryonic kidney (HEK) 293H cells was used to produce rFVIIIFc. Validation studies evaluated identity, purity, activity, and safety. Process-related impurity clearance and viral clearance spiking studies demonstrate robust and reproducible removal of impurities and viruses, with total viral clearance >8–15 log 10 for four model viruses (xenotropic murine leukemia virus, mice minute virus, reovirus type 3, and suid herpes virus 1). Terminal galactose-α-1,3-galactose and N-glycolylneuraminic acid, two non-human glycans, were undetectable in rFVIIIFc. Biochemical and in vitro biological analyses confirmed the purity, activity, and consistency of rFVIIIFc. In conclusion, this manufacturing process produces a highly pure product free of viruses, impurities, and non-human glycan structures, with scale capabilities to ensure a consistent and adequate supply of rFVIIIFc.