Association Between the Medicare Hospice Benefit and Health Care Utilization and Costs for Patients With Poor-Prognosis Cancer

Importance More patients with cancer use hospice currently than ever before, but there are indications that care intensity outside of hospice is increasing, and length of hospice stay decreasing. Uncertainties regarding how hospice affects health care utilization and costs have hampered efforts to promote it. Objective To compare utilization and costs of health care for patients with poor-prognosis cancers enrolled in hospice vs similar patients without hospice care. Design, Setting, and Participants Matched cohort study of patients in hospice and nonhospice care using a nationally representative 20% sample of Medicare fee-for-service beneficiaries who died in 2011. Patients with poor-prognosis cancers (eg, brain, pancreatic, metastatic malignancies) enrolled in hospice before death were matched to similar patients who died without hospice care. Exposures Period between hospice enrollment and death for hospice beneficiaries, and the equivalent period of nonhospice care before death for matched nonhospice patients. Main Outcomes and Measures Health care utilization including hospitalizations and procedures, place of death, cost trajectories before and after hospice start, and cumulative costs, all during the last year of life. Results Among 86 851 patients with poor-prognosis cancers, median time from first poor-prognosis diagnosis to death was 13 months (interquartile range [IQR], 3-34), and 51 924 patients (60%) entered hospice before death. Matching yielded a cohort balanced on age, sex, region, time from poor-prognosis diagnosis to death, and baseline care utilization, with 18 165 patients in the hospice group and 18 165 in the nonhospice group. After matching, 11% of nonhospice and 1% of hospice beneficiaries who had cancer-directed therapy after exposure were excluded. Median hospice duration was 11 days. After exposure, nonhospice beneficiaries had significantly more hospitalizations (65% [95% CI, 64%-66%], vs hospice with 42% [95% CI, 42%-43%]; risk ratio, 1.5 [95% CI, 1.5-1.6]), intensive care (36% [95% CI, 35%-37%], vs hospice with 15% [95% CI, 14%-15%]; risk ratio, 2.4 [95% CI, 2.3-2.5]), and invasive procedures (51% [95% CI, 50%-52%], vs hospice with 27% [95% CI, 26%-27%]; risk ratio, 1.9 [95% CI, 1.9-2.0]), largely for acute conditions not directly related to cancer; and 74% (95% CI, 74%-75%) of nonhospice beneficiaries died in hospitals and nursing facilities compared with 14% (95% CI, 14%-15%) of hospice beneficiaries. Costs for hospice and nonhospice beneficiaries were not significantly different at baseline, but diverged after hospice start. Total costs over the last year of life were $71 517 (95$70 543-72 490) for nonhospice and $62 819 (95$62 082-63 557) for hospice, a statistically significant difference of $8697 (95$7560-$9835). Conclusions and Relevance In this sample of Medicare fee-for-service beneficiaries with poor-prognosis cancer, those receiving hospice care vs not (control), had significantly lower rates of hospitalization, intensive care unit admission, and invasive procedures at the end of life, along with significantly lower total costs during the last year of life.Economic

Genetic Drivers of Kidney Defects in the DiGeorge Syndrome

Background The DiGeorge syndrome, the most common of the microdeletion syndromes, affects multiple organs, including the heart, the nervous system, and the kidney. It is caused by deletions on chromosome 22q11.2; the genetic driver of the kidney defects is unknown. Methods We conducted a genomewide search for structural variants in two cohorts: 2080 patients with congenital kidney and urinary tract anomalies and 22,094 controls. We performed exome and targeted resequencing in samples obtained from 586 additional patients with congenital kidney anomalies. We also carried out functional studies using zebrafish and mice. Results We identified heterozygous deletions of 22q11.2 in 1.1% of the patients with congenital kidney anomalies and in 0.01% of population controls (odds ratio, 81.5; P=4.5×10(-14)). We localized the main drivers of renal disease in the DiGeorge syndrome to a 370-kb region containing nine genes. In zebrafish embryos, an induced loss of function in snap29, aifm3, and crkl resulted in renal defects; the loss of crkl alone was sufficient to induce defects. Five of 586 patients with congenital urinary anomalies had newly identified, heterozygous protein-altering variants, including a premature termination codon, in CRKL. The inactivation of Crkl in the mouse model induced developmental defects similar to those observed in patients with congenital urinary anomalies. Conclusions We identified a recurrent 370-kb deletion at the 22q11.2 locus as a driver of kidney defects in the DiGeorge syndrome and in sporadic congenital kidney and urinary tract anomalies. Of the nine genes at this locus, SNAP29, AIFM3, and CRKL appear to be critical to the phenotype, with haploinsufficiency of CRKL emerging as the main genetic driver. (Funded by the National Institutes of Health and others.)

Managing Digital Assets: Planning the Digital Future of NIST

Susan Makar is a research consultant and knowledge management librarian in the Information Services Division at the National Institute of Standards and Technology in Gaithersburg, MD. She holds an M.A. in library and information science from the University of Iowa. As Web Manager, she is responsible for the overall design and management of ISD’s Web sites, including the NIST Virtual Library (NVL) and the NIST Virtual Museum (NVM). She is currently leading ISD’s effort to determine how best to manage NIST’s digital assets.The Information Services Division (ISD) at the National Institute of Standards and Technology (NIST) is currently studying its needs for managing all aspects of its existing and future digital content. A team of staff tasked with determining how best to manage NIST’s digital assets will discuss their work and progress

Transcriptional effects of a lupus-associated polymorphism in the 5' untranslated region (UTR) of human complement receptor 2 (CR2/CD21)

Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a strong genetic component that determines risk. A common three single-nucleotide polymorphism (SNP) haplotype of the complement receptor 2 (CR2) gene has been associated with increased risk of SLE (Wu et al., 2007; Douglas et al., 2009), and a less common haplotype consisting of the major allele at SNP1 and minor alleles at SNP2 and 3 confers protection (Douglas et al., 2009). SNP1 (rs3813946), which is located in the 5' untranslated region (UTR) of the CR2 gene, altered transcriptional activity of a CR2 promoter-luciferase reporter gene construct transiently transfected into a B cell line (Wu et al., 2007) and had an independent effect in the protective haplotype (Douglas et al., 2009). In this study, we show that this SNP alters transcriptional activity in a transiently transfected non B-cell line as well as in stably transfected cell lines, supporting its relevance in vivo. Furthermore, the allele at this SNP affects chromatin accessibility of the surrounding sequence and transcription factor binding. These data confirm the effects of rs3813946 on CR2 transcription, identifying the 5' UTR to be a novel regulatory element for the CR2 gene in which variation may alter gene function and modify the development of lupus