ABSTRACT
Heart failure causes significant health and financial burdens for patients and society. Multidisciplinary management program (MMP) and exercise training program (ETP) have been reported as cost-effective in improving health outcomes, yet no study has compared the 2 programs. We constructed a Markov model to simulate life year (LY) gained and total costs in usual care (UC), MMP, and ETP. The probability of transitions between states and healthcare costs were extracted from previous literature. We calculated the incremental cost-effectiveness ratio (ICER) over a 10-year horizon. Model robustness was assessed through 1-way and probabilistic sensitivity analyses. The expected LY for patients treated with UC, MMP, and ETP was 7.6, 8.2, and 8.4 years, respectively. From a societal perspective, the expected cost of MMP was $20,695, slightly higher than the cost of UC ($20,092). The cost of ETP was much higher ($48,378) because of its high implementation expense and the wage loss it incurred. The ICER of MMP versus UC was $976 per LY gained, and the ICER of ETP versus MMP was $165,702 per LY gained. The results indicated that, under current cost-effectiveness threshold, MMP is cost-effective compared with UC, and ETP is not cost-effective compared with MMP. However, ETP is cost-effective compared with MMP from a healthcare payer's perspective.
Subject(s)
Disease Management , Exercise Therapy/economics , Forecasting , Health Care Costs , Heart Failure/rehabilitation , Cost-Benefit Analysis , Follow-Up Studies , Heart Failure/economics , Heart Failure/mortality , Hospital Mortality/trends , Humans , Markov Chains , Quality-Adjusted Life Years , Survival Rate/trends , United States/epidemiologyABSTRACT
During pregnancy, both the mother and fetus are vulnerable to environmental pollution by particulate matters and chemicals. Although the toxicity of free pollutants has been frequently reported, the impact of nanoparticle/pollutant adducts on the vulnerable pregnant population remains unclear. In this study, pregnant mice were orally exposed to Mg(OH)2 nanoflakes and nanoflakes adsorbed with Cr(VI) anions during the peri-implantation and organogenesis stages of pregnancy at doses that did not induce systemic toxicity or pregnancy complications. The nano-Mg(OH)2/Cr(VI) adducts formation reduced fetal developmental toxicity compared with the toxicity induced by the same concentration of free Cr(VI) anions.
Subject(s)
Chromium/chemistry , Chromium/toxicity , Magnesium Hydroxide/chemistry , Nanostructures/chemistry , Adsorption , Animals , Bone Development/drug effects , Bone and Bones/drug effects , Bone and Bones/embryology , Chromium/administration & dosage , Chromium/pharmacokinetics , Endoplasmic Reticulum/drug effects , Female , Fetal Development/drug effects , Hyperplasia/chemically induced , Magnesium Hydroxide/administration & dosage , Magnesium Hydroxide/pharmacokinetics , Mice, Inbred ICR , Mitochondria/drug effects , Nanostructures/administration & dosage , Placenta/drug effects , Placenta/pathology , Placenta Growth Factor , Pregnancy , Pregnancy Proteins/blood , Pregnancy Proteins/metabolism , Tissue Distribution , Vascular Endothelial Growth Factor A/blood , Vascular Endothelial Growth Factor A/metabolismABSTRACT
Chronic exposure to carbon disulfide (CS2) can induce polyneuropathy in occupational worker and experimental animals, but underlying mechanism for CS2 neuropathy is currently unknown. In the present study, male Wistar rats were randomly divided into three experimental groups and one control group. The rats in experimental groups were treated with CS2 by gavage at dosages of 200, 400 and 600 mg/kg/day respectively, six times per week for 6 weeks. The formation of autophagosomes and lysosomes in motor neurons of rat spinal cord was observed by transmission electron microscopy, the level of autophagy-related proteins, lysosome-associated membrane protein 1 (LAMP-1), and cathepsin B in spinal cord tissues was determined by Western blot analysis, and the activity of cathepsin B was measured by fluorescence assay. The results demonstrated that the number of lysosomes in motor neurons was markedly increased in CS2-treated rats. In the meantime, the administration of CS2 significantly increased the level of microtubule-associated protein light chain 3-II (LC3-II), Atg1, UVRAG and LAMP-1 in rat spinal cord. Furthermore, the content and activity of cathepsin B in rat spinal cord also showed a significant elevation. Taken together, this study suggested that CS2 intoxication was associated with the activation of lysosomal degradative machinery, which might play a protective role against CS2-induced neuronal damage.
Subject(s)
Autophagy/physiology , Carbon Disulfide/metabolism , Lysosomes/metabolism , Motor Neurons/metabolism , Spinal Cord/metabolism , Animals , Carbon Disulfide/toxicity , Cathepsin B/analysis , Cathepsin B/metabolism , Gait/drug effects , Immunoblotting , Lysosomal Membrane Proteins/analysis , Lysosomal Membrane Proteins/metabolism , Male , Microscopy, Electron, Transmission , Microtubule-Associated Proteins/analysis , Microtubule-Associated Proteins/metabolism , Motor Neurons/ultrastructure , Random Allocation , Rats, Wistar , Spinal Cord/ultrastructureABSTRACT
Carbon disulfide (CS2) may lead to spontaneous abortion and very early pregnancy loss in women exposed in the workplace, but the mechanism remains unclear. We designed an animal model in which gestating Kunming strain mice were exposed to CS2 via i.p. on gestational day 4 (GD4). We found that the number of implanted blastocysts on GD8 was significantly reduced by each dose of 0.1 LD50 (157.85 mg/kg), 0.2 LD50 (315.7 mg/kg) and 0.4 LD50 (631.4 mg/kg). In addition, both the level of DNA damage and apoptosis rates of endometrial cells on GD4.5 were increased, showed definite dose-response relationships, and inversely related to the number of implanted blastocysts. The expressions of mRNA and protein for the Bax and caspase-3 genes in the uterine tissues on GD4.5 were up-regulated, while the expressions of mRNA and protein for the Bcl-2 gene were dose-dependently down-regulated. Our results indicated that DNA damage and apoptosis of endometrial cells were important reasons for the loss of implanted blastocysts induced by CS2.
