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.     

Prokaryotic assemblages and metagenomes in pelagic zones of the South China Sea

Background

Prokaryotic microbes, the most abundant organisms in the ocean, are remarkably diverse. Despite numerous studies of marine prokaryotes, the zonation of their communities in pelagic zones has been poorly delineated. By exploiting the persistent stratification of the South China Sea (SCS), we performed a 2-year, large spatial scale (10, 100, 1000, and 3000 m) survey, which included a pilot study in 2006 and comprehensive sampling in 2007, to investigate the biological zonation of bacteria and archaea using 16S rRNA tag and shotgun metagenome sequencing.

Results

Alphaproteobacteria dominated the bacterial community in the surface SCS, where the abundance of Betaproteobacteria was seemingly associated with climatic activity. Gammaproteobacteria thrived in the deep SCS, where a noticeable amount of Cyanobacteria were also detected. Marine Groups II and III Euryarchaeota were predominant in the archaeal communities in the surface and deep SCS, respectively. Bacterial diversity was higher than archaeal diversity at all sampling depths in the SCS, and peaked at mid-depths, agreeing with the diversity pattern found in global water columns. Metagenomic analysis not only showed differential %GC values and genome sizes between the surface and deep SCS, but also demonstrated depth-dependent metabolic potentials, such as cobalamin biosynthesis at 10 m, osmoregulation at 100 m, signal transduction at 1000 m, and plasmid and phage replication at 3000 m. When compared with other oceans, urease at 10 m and both exonuclease and permease at 3000 m were more abundant in the SCS. Finally, enriched genes associated with nutrient assimilation in the sea surface and transposase in the deep-sea metagenomes exemplified the functional zonation in global oceans.

Conclusions

Prokaryotic communities in the SCS stratified with depth, with maximal bacterial diversity at mid-depth, in accordance with global water columns. The SCS had functional zonation among depths and endemically enriched metabolic potentials at the study site, in contrast to other oceans.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1434-3) contains supplementary material, which is available to authorized users.     

Modulation of Sonic hedgehog signaling and WW domain containing oxidoreductase WOX1 expression enhances radiosensitivity of human glioblastoma cells

WW domain containing oxidoreductase, designated WWOX, FOR or WOX1, is a known pro-apoptotic factor when ectopically expressed in various types of cancer cells, including glioblastoma multiforme (GBM). The activation of sonic hedgehog (Shh) signaling, especially paracrine Shh secretion in response to radiation, is associated with impairing the effective irradiation of cancer cells. Here, we examined the role of Shh signaling and WOX1 overexpression in the radiosensitivity of human GBM cells. Our results showed that ionizing irradiation (IR) increased the cytoplasmic Shh and nuclear Gli-1 content in GBM U373MG and U87MG cells. GBM cells with exogenous Shh treatment exhibited similar results. Pretreatment with Shh peptides protected U373MG and U87MG cells against IR in a dose-dependent manner. Cyclopamine, a Hedgehog/Smoothened (SMO) inhibitor, reversed the protective effect of Shh in U87MG cells. Cyclopamine increased Shh plus IR-induced H2AX, a marker of DNA double-strand breaks, in these cells. To verify the role of Shh signaling in the radiosensitivity of GBM cells, we tested the effect of the Gli family zinc finger 1 (Gli-1) inhibitor zerumbone and found that it could sensitize GBM cells to IR. We next examined the role of WOX1 in radiosensitivity. Overexpression of WOX1 enhanced the radiosensitivity of U87MG (possessing wild type p53 or WTp53) but not U373MG (harboring mutant p53 or MTp53) cells. Pretreatment with Shh peptides protected both WOX1-overexpressed U373MG and U87MG cells against IR and increased the cytoplasmic Shh and nuclear Gli-1 content. Zerumbone enhanced the radiosensitivity of WOX1-overexpressed U373MG and U87MG cells. In conclusion, overexpression of WOX1 preferentially sensitized human GBM cells possessing wild type p53 to radiation therapy. Blocking of Shh signaling may enhance radiosensitivity independently of the expression of p53 and WOX1. The crosstalk between Shh signaling and WOX1 expression in human glioblastoma warrants further investigation.     

Beneficial effects of co-treatment with dextromethorphan on prenatally methadone-exposed offspring

Background

Heroin use among young women of reproductive age has drawn much attention around the world. Although methadone is widely used in maintenance therapy for heroin/morphine addiction, the long-term effects of prenatal exposure to methadone and preventative therapy remain unclear. For revealing this question, female pregnant Sprague–Dawley rats were sub-grouped to receive (1) vehicle, (2) methadone 5 mg/kg at embryonic day 3 (E3) and then 7 mg/kg from E4 to E20, (3) dextromethorphan (DM) 3 mg/kg, and (4) methadone + DM (the rats received methadone followed by DM treatment), subcutaneously, twice a day from E3 to E20. The body weight, natural withdrawal, pain sensitivity, ED50, conditioned place preference and water maze were conducted at different postnatal stages (P1 to P79) of offspring. The quantitative real-time RT-PCR and electrophysiology were also used to measure the gene expression of opioid receptors in the spinal cord and changes of LTP/LTD in the hippocampus, separately.

Results

Prenatal exposure to methadone or DM did not affect survival rate, body weight, water maze and LTP or LTD of offspring. However, prenatal methadone significantly increased the withdrawal symptoms, pain sensitivity, addiction liability and decreased the mRNA expression of pain related opioid receptors. Co-administration of DM with methadone in the maternal rats effectively prevented these abnormalities of offspring induced by methadone.

Conclusions

Our study clearly showed that co-administration of dextromethorphan with methadone in the maternal rats prevented the adverse effects induced by prenatal methadone exposure. It implies that dextromethorphan may have a potential to be used in combination with methadone for maintenance treatment in pregnant heroin-addicted women to prevent the adverse effects induced by methadone on offspring.

Electronic supplementary material

The online version of this article (doi:10.1186/s12929-015-0126-2) contains supplementary material, which is available to authorized users.     

Pentoxifylline Attenuates Proteinuria in Anti-Thy1 Glomerulonephritis via Downregulation of Nuclear Factor-κB and Smad2/3 Signaling

Anti-Thy1 glomerulonephritis is a rat nephritis model closely simulating human mesangial proliferative glomerulonephritis. It affects primarily the mesangium, yet displays substantial proteinuria during the course. This study investigated the molecular signals underlying proteinuria in this disease and the modulation of which by the known antiproteinuric agent, pentoxifylline. Male Wistar rats were randomly divided into a control group and nephritic groups with or without treatment with IMD-0354 (an IκB kinase inhibitor), SB431542 (an activin receptor–like kinase inhibitor) or pentoxifylline. Kidney sections were prepared for histological examinations. Glomeruli were isolated for mRNA and protein analysis. Urine samples were collected for protein and nephrin quantitation. One day after nephritis induction, proteinuria developed together with ultrastructural changes of the podocyte and downregulation of podocyte mRNA and protein expression. These were associated with upregulation of tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β/activins mRNAs and activation of nuclear factor (NF)-κB p65 and Smad2/3. IMD-0354 attenuated proteinuria on d 1, whereas SB431542 decreased proteinuria on d 3 and 5, in association with partial restoration of downregulated podocyte mRNA and protein expression. Pentoxifylline attenuated proteinuria and nephrinuria through the course, plus inhibition of p-NF-κB p65 (d 1) and p-Smad2/3 (d 5) and partial reversal of downregulated podocyte mRNA and protein. Our data show that the pathogenesis of proteinuria in anti-Thy1 glomerulonephritis involves TNF-α and TGF-β/activin pathways, and the evolution of this process can be attenuated by pentoxifylline via downregulation of NF-κB and Smad signals and restoration of the podocyte component of the glomerular filtration barrier.     

Impacts of Autophagy-Inducing Ingredient of Areca Nut on Tumor Cells

Areca nut (AN) is a popular carcinogen used by about 0.6-1.2 billion people worldwide. Although AN contains apoptosis-inducing ingredients, we previously demonstrated that both AN extract (ANE) and its 30-100 kDa fraction (ANE 30-100K) predominantly induce autophagic cell death in both normal and malignant cells. In this study, we further explored the action mechanism of ANE 30-100K-induced autophagy (AIA) in Jurkat T lymphocytes and carcinoma cell lines including OECM-1 (mouth), CE81T/VGH (esophagus), SCC25 (tongue), and SCC-15 (tongue). The results showed that chemical- and small hairpin RNA (shRNA)-mediated inhibition of AMP-activated protein kinase (AMPK) resulted in the attenuation of AIA in Jurkat T but not in OECM-1 cells. Knockdown of Atg5 and Beclin 1 expressions ameliorated AIA in OECM-1/CE81T/VGH/Jurkat T and OECM-1/SCC25/SCC-15, respectively. Furthermore, ANE 30-100K could activate caspase-3 after inhibition of Beclin 1 expression in OECM-1/SCC25/SCC15 cells. Meanwhile, AMPK was demonstrated to be the upstream activator of the extracellular-regulated kinase (ERK) in Jurkat T cells, and inhibition of MEK attenuated AIA in Jurkat T/OECM-1/CE81T/VGH cells. Finally, we also found that multiple myeloma RPMI8226, lymphoma U937, and SCC15 cells survived from long-term non-cytotoxic ANE 30-100K treatment exhibited stronger resistance against serum deprivation through upregulated autophagy. Collectively, our studies indicate that Beclin-1 and Atg5 but not AMPK are commonly required for AIA, and MEK/ERK pathway is involved in AIA. Meanwhile, it is also suggested that long-term AN usage might increase the resistance of survived tumor cells against serum-limited conditions.     

Extreme Levels of HbA1c Increase Incident ESRD Risk in Chinese Patients with Type 2 Diabetes: Competing Risk Analysis in National Cohort of Taiwan Diabetes Study

Background

Whether HbA1c is a predictor of end-stage renal disease (ESRD) in type 2 diabetes patients remains unclear. This study evaluated relationship between HbA1c and ESRD in Chinese patients with type 2 diabetes.

Methods

Patients aged ≥ 30 years who were free of ESRD (n = 51 681) were included from National Diabetes Care Management Program from 2002–2003. Extended Cox proportional hazard model with competing risk of death served to evaluate association between HbA1c level and ESRD.

Results

A total of 2613 (5.06%) people developed ESRD during a follow-up period of 8.1 years. Overall incidence rate of ESRD was 6.26 per 1000 person-years. Patients with high levels of HbA1c had a high incidence rate of ESRD, from 4.29 for HbA1c of  6.0%–6.9% to 10.33 for HbA1c ≥ 10.0% per 1000 person-years. Patients with HbA1c < 6.0% particularly had a slightly higher ESRD incidence (4.34 per 1000 person-years) than those with HbA1c  of 6.0%–6.9%. A J-shaped relationship between HbA1c level and ESRD risk was observed. After adjustment, patients with HbA1c < 6.0% and ≥ 10.0% exhibited an increased risk of ESRD (HR: 1.99, 95% CI: 1.62–2.44; HR: 4.42, 95% CI: 3.80–5.14, respectively) compared with those with HbA1c of 6.0%–6.9%.

Conclusions

Diabetes care has focused on preventing hyperglycemia, but not hypoglycemia. Our study revealed that HbA1c level ≥ 7.0% was linked with increased ESRD risk in type 2 diabetes patients, and that HbA1c < 6.0% also had the potential to increase ESRD risk. Our study provides epidemiological evidence that appropriate glycemic control is essential for diabetes care to meet HbA1c targets and improve outcomes without increasing the risk to this population. Clinicians need to pay attention to HbA1c results on diabetic nephropathy.