The Role of a Self-management Program in the Control of Mild to Moderate Asthma: a Randomized Controlled Study

Background: Asthma patient education has been recognized as an important component of asthma control. The aim of the present study was to carry out a cost-effectiveness analysis of patient education in patients with mild to moderate asthma during 6 months of follow up. Methods: We randomly allocated asthma patients who were covered by health insurance to a control group (group C) or a self-management group (group S). Self-management consisted of measurement of peak expiratory flow (PEF) and monthly individual education and advice by a specialist. Effectiveness was evaluated on the basis of PEF, quality of life, and mean total cost of medical expenses. Furthermore, we asked the patients about symptom improvement and their level of satisfaction with this program. Results: PEF values in group S gradually increased at 3 months after the self-management program and remained at high levels. The total costs decreased by 30% from baseline in group S, whereas they increased by 15% in group C. The cost of one-day visits showed no difference between the two groups, but the frequency of visits to general practitioners decreased in group S as compared with group C. Furthermore, the number of episodes of asthma attacks decreased in group S but not in group C, and 94% of the group S patients replied that they considered the self-management program to have been useful. Conclusions: We conclude that an individual self-management program is not only a safe and effective aid in the treatment of mild to moderate asthma but can also reduce medical expenses

Selective Detection of Intracellular Drug Metabolism by Metal-Organic Framework-Coated Plasmonic Nanowire

Unveiling intracellular drug metabolism is crucial for improving drug development, which requires real-time detection with molecular selectivity in the intracellular environment. Surface-enhanced Raman scattering (SERS) with metal nanoparticles enables the detection of molecules in living cells, but after entering the cells, most nanoparticles are captured into vesicles, limiting the SERS detection inside these compartments. Moreover, the identification of the target signal in the complex intracellular environment is challenging due to Raman fingerprints from endogenous material interfering with the drug signal. To overcome these issues, here the coating of a silver nanowire with zeolitic imidazolate framework-8 (ZIF-8) as a novel endoscopic probe with molecular selectivity to investigate the location and metabolism in cells of a common anticancer drug, irinotecan, is reported. Irinotecan in cells is metabolized by carboxylesterase to form SN-38, which inhibits topoisomerase I and DNA synthesis. Thanks to the molecular selectivity of ZIF-8, the endoscopic probe selectively adsorbs and detects SERS signal of SN-38 over irinotecan. This selectivity enables monitoring of the conversion of irinotecan into SN-38 and following its intracellular location over time. This work clearly shows the potential of metal-organic framework-coated nanowire endoscopy to specifically track drug molecules and explore their metabolism in cells

Long-term survival of patients receiving home hemodialysis with self-punctured arteriovenous access.

ObjectiveTo determine the long-term survival of patients receiving home hemodialysis (HHD) through self-punctured arteriovenous access.MethodsWe conducted an observational study of all patients receiving HHD at our facility between 2001 and 2020. The primary outcome was treatment survival, and it was defined as the duration from HHD initiation to the first event of death or technique failure. The secondary outcomes were the cumulative incidence of technique failure and mortality. Cox proportional hazard models were used to identify the predictive factors for treatment survival.ResultsA total of 77 patients (mean age, 50.7 years; 84.4% male; 23.4% with diabetes) were included. The median dialysis duration was 18 hours per week, and all patients self-punctured their arteriovenous fistula. During a median follow-up of 116 months, 30 treatment failures (11 deaths and 19 technique failures) were observed. The treatment survival was 100% at 1 year, 83.5% at 5 years, 67.2% at 10 years, and 34.6% at 15 years. Age (adjusted hazard ratio [aHR], 1.07) and diabetes (aHR, 2.45) were significantly associated with treatment survival. Cardiovascular disease was the leading cause of death, and vascular access-related issues were the primary causes of technique failure, which occurred predominantly after 100 months from HHD initiation.ConclusionThis study showed a favorable long-term prognosis of patients receiving HHD. HHD can be a sustainable form of long-term kidney replacement therapy. However, access-related technique failures occur more frequently in patients receiving it over the long term. Therefore, careful management of vascular access is crucial to enhance technique survival

A novel β-sheet breaker, RS-0406, reverses amyloid β-induced cytotoxicity and impairment of long-term potentiation in vitro

1. Fibril formation of amyloid β peptide (Aβ) is considered to be responsible for the pathology of Alzheimer's disease (AD). The Aβ fibril is formed by a protein misfolding process in which intermolecular β-sheet interactions become stabilized abnormally. Thus, to develop potential anti-AD drugs, we screened an in-house library to find compounds which have a profile as a β-sheet breaker. 2. We searched for a β-sheet breaker profile in an in-house library of approximately 113,000 compounds. From among the screening hits, we focused on N,N′-bis(3-hydroxyphenyl)pyridazine-3,6-diamine (named RS-0406), which had been newly synthesized in our laboratory. This compound (10–100 μg ml(−1)) was found to be capable of significantly inhibiting 25 μM Aβ(1–42) fibrillogenesis and, furthermore, disassembling preformed Aβ(1–42) fibrils in vitro. 3. We then investigated the effect of RS-0406 on 111 nM Aβ(1–42)-induced cytotoxicity in primary hippocampal neurons, and found that 0.3–3 μg ml(−1) RS-0406 ameliorates the cytotoxicity. Moreover, 3 μg ml(−1) RS-0406 reversed 1 μM Aβ(1–42)-induced impairment of long-term potentiation in hippocampal slices. 4. In this study, we have succeeded in identifying RS-0406 which has potential to inhibit Aβ(1–42) fibrillogenesis, and to protect neurons against Aβ(1–42)-induced biological toxicity in vitro. These results suggest that RS-0406 or one of the derivatives could become a therapeutic agent for AD patients