The Impact of Hospice Care on Survival and Healthcare Costs for Patients with Lung Cancer: A National Longitudinal Population-Based Study in Taiwan

Background

The healthcare costs of cancer care are highest in the last month of life. The effect of hospice care on end-of-life (EOL) healthcare costs is not clearly understood.

Purpose

The purpose of this study was to evaluate the effect of hospice care on survival and healthcare costs for lung cancer patients in their final month of life.

Methods

We adopted Taiwan’s National Health Insurance Research Claims Database to analyze data for 3399 adult lung cancer patients who died in 1997–2011. A logistic regression analysis was performed to determine the predictors of high healthcare cost, defined as costs falling above the 90th percentile. Patients who received hospice cares were assigned to a hospice (H) group and those who did not were assigned to a non-hospice (non-H) group.

Results

The patients in the H group had a longer mean (median) survival time than those in the non-H group did (1.40 ± 1.61 y (0.86) vs. 1.10 ± 1.47 (0.61), p<0.001). The non-H group had a lower mean healthcare cost than the H group (US $1,821 ± 2,441 vs. US $1,839 ± 1,638, p<0.001). And, there were a total of 340 patients (10%) with the healthcare costs exceeding the 90th percentile (US $4,721) as the cutoff value of high cost. The non-H group had a higher risk of high cost than the H group because many more cases in the non-H group had lower costs. Moreover, the risk of high health care costs were predicted for patients who did not receive hospice care (odds ratio [OR]: 3.68, 95% confidence interval [CI]: 2.44–5.79), received chemotherapy (OR: 1.51, 95% CI: 1.18–1.96) and intubation (OR: 2.63, 95% CI: 1.64–4.16), and those who had more emergency department visits (OR: 1.78, 95% CI: 1.24–2.52), longer hospital admission in days (OR: 1.08, 95% CI: 1.07–1.09), and received radiotherapy (OR: 1.33, 95% CI: 1.00–1.78). Lower risks of high health care costs were observed in patients with low socioeconomic status (OR: 0.58, 95% CI: 0.40–0.83), or previous employment (OR: 0.66, 95% CI: 0.47–0.92). After propensity-score matching, the patients of the non-H group had a higher mean cost and a higher risk of high cost. Similar results were obtained from logistic regression analysis in propensity score-matched patients.

Conclusions

The survival of the hospice group was longer than non-H group, and patients in the non-H group were 3.74 times more likely to have high healthcare costs at EOL. The positive predictors for high health care costs were patients who did not receive hospice care, who received chemotherapy and intubation, who had more emergency department visits and longer hospital admission, and who received radiotherapy. Negative predictors were patients who had a low socioeconomic status or previous employment. The issue of how to reduce the high health care costs for patients with lung cancer in the last month of life is a challenge for policy makers and health care providers.     

A Robust GWSS Method to Simultaneously Detect Rare and Common Variants for Complex Disease

The rapid advances in sequencing technologies and the resulting next-generation sequencing data provide the opportunity to detect disease-associated variants with a better solution, in particular for low-frequency variants. Although both common and rare variants might exert their independent effects on the risk for the trait of interest, previous methods to detect the association effects rarely consider them simultaneously. We proposed a class of test statistics, the generalized weighted-sum statistic (GWSS), to detect disease associations in the presence of common and rare variants with a case-control study design. Information of rare variants was aggregated using a weighted sum method, while signal directions and strength of the variants were considered at the same time. Permutations were performed to obtain the empirical p-values of the test statistics. Our simulation showed that, compared to the existing methods, the GWSS method had better performance in most of the scenarios. The GWSS (in particular VDWSS-t) method is particularly robust for opposite association directions, association strength, and varying distributions of minor-allele frequencies. It is therefore promising for detecting disease-associated loci. For empirical data application, we also applied our GWSS method to the Genetic Analysis Workshop 17 data, and the results were consistent with the simulation, suggesting good performance of our method. As re-sequencing studies become more popular to identify putative disease loci, we recommend the use of this newly developed GWSS to detect associations with both common and rare variants.     

Large amounts of labile organic carbon in permafrost soils of northern Alaska

Permafrost‐affected soils of the northern circumpolar region represent 50% of the terrestrial soil organic carbon (SOC) reservoir and are most strongly affected by climatic change. There is growing concern that this vast SOC pool could transition from a net C sink to a source. But so far little is known on how the organic matter (OM) in permafrost soils will respond in a warming future, which is governed by OM composition and possible stabilization mechanisms. To investigate if and how SOC in the active layer and adjacent permafrost is protected against degradation, we employed density fractionation to separate differently stabilized SOM fractions. We studied the quantity and quality of OM in different compartments using elemental analysis, ¹³C solid‐phase nuclear magnetic resonance (¹³C‐NMR) spectroscopy, and ¹⁴C analyses. The soil samples were derived from 16 cores from drained thaw lake basins, ranging from 0 to 5500 years of age, representing a unique series of developing Arctic soils over time. The normalized SOC stocks ranged between 35.5 and 86.2 kg SOC m^?3, with the major amount of SOC located in the active layers. The SOC stock is dominated by large amounts of particulate organic matter (POM), whereas mineral‐associated OM especially in older soils is of minor importance on a mass basis. We show that tremendous amounts of over 25 kg OC per square meter are stored as presumably easily degradable OM rich in carbohydrates. Only about 10 kg OC per square meter is present as presumably more stable, mineral‐associated OC. Significant amounts of the easily degradable, carbohydrate‐rich OM are preserved in the yet permanently frozen soil below the permafrost table. Forced by global warming, this vast labile OM pool could soon become available for microbial degradation due to the continuous deepening of the annually thawing active layer.     

Xanthine-based KMUP-1 improves HDL via PPARγ/SR-B1, LDL via LDLRs,and HSL via PKA/PKG for hepatic fat loss

The phosphodiesterase inhibitor (PDEI)/eNOS enhancer KMUP-1, targeting G-protein coupled receptors (GPCRs), improves dyslipidemia. We compared its lipid-lowering effects with simvastatin and explored hormone-sensitive lipase (HSL) translocation in hepatic fat loss. KMUP-1 HCl (1, 2.5, and 5 mg/kg/day) and simvastatin (5 mg/kg/day) were administered in C57BL/6J male mice fed a high-fat diet (HFD) by gavage for 8 weeks. KMUP-1 inhibited HFD-induced plasma/liver TG, total cholesterol, and LDL; increased HDL/3-hydroxy-3-methylglutaryl-CoA reductase (HMGR)/Rho kinase II (ROCK II)/PPARγ/ABCA1; and decreased liver and body weight. KMUP-1 HCl in drinking water (2.5 mg/200 ml tap water) for 1–14 or 8–14 weeks decreased HFD-induced liver and body weight and scavenger receptor class B type I expression and increased protein kinase A (PKA)/PKG/LDLRs/HSL expression and immunoreactivity. In HepG2 cells incubated with serum or exogenous mevalonate, KMUP-1 (10⁻⁷∼10⁻⁵ M) reversed HMGR expression by feedback regulation, colocalized expression of ABCA1/apolipoprotein A-I/LXRα/PPARγ, and reduced exogenous geranylgeranyl pyrophosphate/farnesyl pyrophosphate (FPP)-induced RhoA/ROCK II expression. A guanosine 3′,5′-cyclic monophosphate (cGMP) antagonist reversed KMUP-1-induced ROCK II reduction, indicating cGMP/eNOS involvement. KMUP-1 inceased PKG and LDLRs surrounded by LDL and restored oxidized LDL-induced PKA expresion. Unlike simvastatin, KMUP-1 could not inhibit ¹⁴C mevalonate formation. KMUP-1 could, but simvastatin could not, decrease ROCK II expression by exogenous FPP/CGPP. KMUP-1 improves HDL via PPARγ/LXRα/ABCA1/Apo-I expression and increases LDLRs/PKA/PKG/HSL expression and immunoreactivity, leading to TG hydrolysis to lower hepatic fat and body weight.     

Subgenomic promoter recognition by the norovirus RNA-dependent RNA polymerases

The replication enzyme of RNA viruses must preferentially recognize their RNAs in an environment that contains an abundance of cellular RNAs. The factors responsible for specific RNA recognition are not well understood, in part because viral RNA synthesis takes place within enzyme complexes associated with modified cellular membrane compartments. Recombinant RNA-dependent RNA polymerases (RdRps) from the human norovirus and the murine norovirus (MNV) were found to preferentially recognize RNA segments that contain the promoter and a short template sequence for subgenomic RNA synthesis. Both the promoter and template sequence contribute to stable RdRp binding, accurate initiation of the subgenomic RNAs and efficient RNA synthesis. Using a method that combines RNA crosslinking and mass spectrometry, residues near the template channel of the MNV RdRp were found to contact the hairpin RNA motif. Mutations in the hairpin contact site in the MNV RdRp reduced MNV replication and virus production in cells. This work demonstrates that the specific recognition of the norovirus subgenomic promoter is through binding by the viral RdRp.     

Physiological Outperformance at the Morphologically-Transformed Edge of the Cyanobacteriosponge Terpios hoshinota (Suberitidae: Hadromerida) when Confronting Opponent Corals

Terpios hoshinota, an encrusting cyanosponge, is known as a strong substrate competitor of reef-building corals that kills encountered coral by overgrowth. Terpios outbreaks cause significant declines in living coral cover in Indo-Pacific coral reefs, with the damage usually lasting for decades. Recent studies show that there are morphological transformations at a sponge’s growth front when confronting corals. Whether these morphological transformations at coral contacts are involved with physiological outperformance (e.g., higher metabolic activity or nutritional status) over other portions of Terpios remains equivocal. In this study, we compared the indicators of photosynthetic capability and nitrogen status of a sponge-cyanobacteria association at proximal, middle, and distal portions of opponent corals. Terpios tissues in contact with corals displayed significant increases in photosynthetic oxygen production (ca. 61%), the δ¹³C value (ca. 4%), free proteinogenic amino acid content (ca. 85%), and Gln/Glu ratio (ca. 115%) compared to middle and distal parts of the sponge. In contrast, the maximum quantum yield (F_v/F_m), which is the indicator usually used to represent the integrity of photosystem II, of cyanobacteria photosynthesis was low (0.256~0.319) and showed an inverse trend of higher values in the distal portion of the sponge that might be due to high and variable levels of cyanobacterial phycocyanin. The inconsistent results between photosynthetic oxygen production and F_v/F_m values indicated that maximum quantum yields might not be a suitable indicator to represent the photosynthetic function of the Terpios-cyanobacteria association. Our data conclusively suggest that Terpios hoshinota competes with opponent corals not only by the morphological transformation of the sponge-cyanobacteria association but also by physiological outperformance in accumulating resources for the battle.     

Primary and secondary effects of ascorbate on procollagen synthesis and protein synthesis by primary cultures of tendon fibroblasts.

The effects of ascorbic acid on collagen biosynthesis were studied in primary cultures of fibroblasts from chick embryo tendons. Addition of ascorbate to the cultures increased the rate of synthesis of procollagen hydroxyproline, but the effect was not explained by activation of prolyl hydroxylase as has been seen in other cell cultures. Instead the increase in the rate of hydroxyproline synthesis appeared to be the result of some direct cofactor effect of the vitamin. In the presence of ascorbate, most of the newly synthesized procollagen was hydroxylated and became triple helical. In the absence of ascorbate, the overall degree of hydroxylation in newly synthesized procollagen was reduced, but a small fraction of newly synthesized procollagen was near-maximally hydroxylated and became triple helical. When cultures were exposed to ascorbic acid for more than 6 h, there was an increase in rate of protein synthesis, rate of procollagen synthesis, and fraction of membrane-bound ribosomes. The increases in these parameters in the presence of ascorbate appeared to be a secondary effect produced by the accumulation of stable triple-helical procollagen in the culture system.     

Cell density-dependent increase in prolyl hydroxylase activity in cultured L-929 cells requires de novo protein synthesis.

Prolyl hydroxylase activity in cultured L-929 cells was found to increase when cells grew from log phase to stationary phase and when cells were harvested at the mid-log phase and replated at higher cell densities. Cycloheximide and actinomycin D inhibited the cell density-dependent increase in prolyl hydroxylase activity indicating that the increase in prolyl hydroxylase activity required de novo synthesis of protein and RNA. Prolyl hydroxylase was purified from cultured L-929 cells and antibodies against the protein were raised in rabbits. The antibodies were used to demonstrate that L-929 cells contained two forms of prolyl hydroxylase: an enzymatically active, tetrameric form consisting of two alpha and two beta polypeptide chains and an enzymatically inactive form containing immunologically cross-reacting protein. The polypeptide chains alpha, beta and cross-reacting protein were obtained by immunoadsorption. Peptide map analysis indicated that cross-reacting protein was similar if not identical to beta in primary structure, and alpha was different from both beta and cross-reacting protein. The results suggested that the prolyl hydroxylase levels in cells or tissues may be regulated by new protein and/or RNA synthesis.