Post-acute care for frail older people decreases 90-day emergency room visits, readmissions and mortality: An interventional study.

BACKGROUND: To evaluate the effects of post-acute care (PAC) on frail older adults after acute hospitalization in Taiwan. METHODS: This was a multicenter interventional study. Frail patients aged ≥ 75 were recruited and divided into PAC or control group. The PAC group received comprehensive geriatric assessment (CGA) and multifactorial intervention including exercise, nutrition education, and medicinal adjustments for two to four weeks, while the control group received only CGA. Outcome measures included emergency room (ER) visits, readmissions, and mortality within 90 days after PAC. RESULTS: Among 254 participants, 205 (87.6±6.0 years) were in the PAC and 49 (85.2±6.0 years) in the control group. PAC for more than two weeks significantly decreased 90-day ER visits (odds ratio [OR] 0.21, 95% confidence interval [CI] 0.10-0.43; p = 0.024), readmissions (OR 0.30, 95% CI 0.16-0.56; p < 0.001), and mortality (OR 0.20, 95% CI 0.04-0.87; p = 0.032). Having problems in self-care was an independent risk factor for 90-day ER visits (OR 2.11, 95% CI 1.17-3.78; p = 0.012), and having problems in usual activities was an independent risk factor for 90-day readmissions (OR 2.69, 95% CI 1.53-4.72; p = 0.001) and mortality (OR 3.16, 95% CI 1.16-8.63; p = 0.024). CONCLUSION: PAC program for more than two weeks could have beneficial effects on decreasing ER visits, readmissions, and mortality after an acute illness in frail older patients. Those who perceived severe problems in self-care and usual activities had a higher risk of subsequent adverse outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT Identifier: NCT05452395.

Comparison of Highly Intensive Home-Based Post-acute Care to Inpatient Program for Patients With Fragility Fractures After Surgery.

Introduction: Evidence suggests that patients with fragility fractures would benefit from post-acute care (PAC); however, they have been subjected to varying PAC programs. This study aimed to compare the effectiveness of home-based PAC (HPAC) to inpatient PAC (IPAC) programs for patients with fragility fractures in Taiwan. Materials and methods: This is a retrospective study that reviewed the medical records of patients who received HPAC or IPAC within three weeks after hip, knee, or spine fragility fractures in the Taipei City Hospital from September 1, 2017, to August 31, 2018. Results: The mean age (78.9 ± 10.8 years) showed significant difference between the HPAC (age = 80.6 ± 11.1, n = 83) and the IPAC (age = 78.2 ± 10.6, n = 185) groups (P = .049). After PAC, both HPAC and IPAC groups showed improvement on Barthel index, numerical pain rating scale, and Harris hip score (all P < .001). Patients in the HPAC group displayed greater improvement than the IPAC group on Barthel Index for activities of daily living (ADLs) by 5.8 (95% confidence interval, 3.0 to 8.5). The IPAC group had a significant longer length of PAC than the HPAC group (12.4 ± 3.0 vs. 11.1 ± 2.7, P < .001). Conclusion: Both PAC programs could significantly improve functional performance and reduce pain in patients with fragility fractures. Patients treated in the HPAC group had better ADLs, and less length of PAC.

Efficacy and cost-effectiveness analysis of post-acute care for elderly patients with hip fractures.

BACKGROUND/PURPOSE: Hip fractures are associated with physical dysfunction, and poor quality of life in the elderly. Post-acute care (PAC) would facilitate functional recovery in patients with hip fractures after surgeries. Taiwan has proposed a nationwide PAC program for hip fractures since 2017, but little has been known about its effectiveness. Therefore, this study aimed to evaluate the efficacy and cost-effectiveness of the PAC program for hip fracture patients in Taiwan. METHODS: This was a prospective study. Patients aged ≥ 65 years with hip fractures after surgeries were recruited and divided into home-based, hospital-based, and control groups. Outcome measures included pain, physical function (sit-to-stand test, Barthel Index [BI], and Harris hip score [HHS]), and quality of life (EuroQol instrument [EQ-5D]). Direct medical and non-medical costs were recorded. Cost-effectiveness ratio (CER) was calculated as the amount of New Taiwanese Dollars (NTDs) paid per BI and EQ-5D unit improvement. RESULTS: Forty-one patients participated in this study, with 17, 12, and 12 in the home-based, hospital-based, and control groups, respectively. The home-based group showed significant improvements in BI and HHS compared to the controls (p = 0.018 and p = 0.029, respectively). The hospital-based group demonstrated significant improvement in EQ-5D compared to the controls (p = 0.015). The home-based PAC program demonstrated the best CER for BI (NTD 554) and EQ-5D (NTD 41948). CONCLUSION: Both PAC programs would significantly improve the physical function and quality of life in patients with hip fractures. However, the home-based PAC provided the best CER for BI and EQ-5D.

A PEGylated hyaluronic acid conjugate for targeted cancer immunotherapy.

The cell-free approach to foreignizing tumor cells with non-self antigens has received increasing attention as a method to induce cytotoxic T lymphocyte (CTL)-mediated immunological rejection of tumors, because the clinical translation of the conventional CTL-based cancer immunotherapies has been limited by a complicated manufacturing process and autotransplantation. In this study, we prepared matrix metalloproteinase 9 (MMP9)-responsive polymeric conjugates consisting of PEGylated hyaluronic acid (HA) as the targeting moiety and ovalbumin (OVA) as the model foreign antigen. The MMP9-cleavable linker was introduced between PEG and the HA backbone to facilitate the detachment of the PEG corona from the conjugate at the tumor site. From the in vitro cellular uptake study, it was revealed that the conjugate was effectively taken up by the CD44-expressing TC-1 cancer cells in the presence of MMP9 via receptor-mediated endocytosis. When the conjugate was systemically administered into the tumor-bearing mice with endogenous OVA-specific CTLs, the tumor growth was markedly inhibited, which was attributed to the significant antigen presentation on the tumor cells. Overall, the MMP9-responsive conjugates bearing foreign antigens might have the potential as an alternative to CTL-based cancer immunotherapeutics.

Gold-stabilized carboxymethyl dextran nanoparticles for image-guided photodynamic therapy of cancer.

Photodynamic therapy (PDT) has been extensively investigated to treat cancer since it induces cell death through the activation of photosensitizers by light. However, its success has been hampered by the insufficient selectivity of photosensitizers to tumor tissues. In an attempt to increase the therapeutic efficacy of PDT by targeting the photosensitizer specifically to the tumor site, we prepared chlorin e6 (Ce6)-loaded gold-stabilized carboxymethyl dextran nanoparticles (Ce6-GS-CNPs). Ce6-GS-CNPs possessed highly stable nanostructures and no significant change was observed in their particle size in the presence of serum for 6 days. When Ce6-GS-CNPs were intravenously injected into tumor-bearing mice, they exhibited prolonged circulation in the body and gradually accumulated in the tumor tissue. Under laser irradiation of the tumor site which could be recognized by the near-infrared fluorescence imaging system, Ce6-GS-CNPs effectively suppressed tumor growth. Overall, Ce6-GS-CNPs might have potential as nanomedicine for image-guided photodynamic cancer therapy.

Gold-Nanoclustered Hyaluronan Nano-Assemblies for Photothermally Maneuvered Photodynamic Tumor Ablation.

Optically active nanomaterials have shown great promise as a nanomedicine platform for photothermal or photodynamic cancer therapies. Herein, we report a gold-nanoclustered hyaluronan nanoassembly (GNc-HyNA) for photothermally boosted photodynamic tumor ablation. Unlike other supramolecular gold constructs based on gold nanoparticle building blocks, this system utilizes the nanoassembly of amphiphilic hyaluronan conjugates as a drug carrier for a hydrophobic photodynamic therapy agent verteporfin, a polymeric reducing agent, and an organic nanoscaffold upon which gold can grow. Gold nanoclusters were selectively installed on the outer shell of the hyaluronan nanoassembly, forming a gold shell. Given the dual protection effect by the hyaluronan self-assembly as well as by the inorganic gold shell, verteporfin-encapsulated GNc-HyNA (Vp-GNc-HyNA) exhibited outstanding stability in the bloodstream. Interestingly, the fluorescence and photodynamic properties of Vp-GNc-HyNA were considerably quenched due to the gold nanoclusters covering the surface of the nanoassemblies; however, photothermal activation by 808 nm laser irradiation induced a significant increase in temperature, which empowered the PDT effect of Vp-GNc-HyNA. Furthermore, fluorescence and photodynamic effects were recovered far more rapidly in cancer cells due to certain intracellular enzymes, particularly hyaluronidases and glutathione. Vp-GNc-HyNA exerted a great potential to treat tumors both in vitro and in vivo. Tumors were completely ablated with a 100% survival rate and complete skin regeneration over the 50 days following Vp-GNc-HyNA treatment in an orthotopic breast tumor model. Our results suggest that photothermally boosted photodynamic therapy using Vp-GNc-HyNA can offer a potent therapeutic means to eradicate tumors.

Zwitterionic mesoporous nanoparticles with a bioresponsive gatekeeper for cancer therapy.

UNLABELLED: To enhance cellular uptake and site-specific drug release in the tumor microenvironment, zwitterionic mesoporous silica nanoparticles (Z-MSN) were prepared by introducing a bioresponsive gatekeeper composed of negatively charged carboxylic groups and positively charged quaternary amine groups. When these Z-MSN encountered a mildly acidic environment, their surface charge readily switched from negative to positive by cleavage of an acid-labile maleic amide linkage, thus allowing for effective cellular uptake into tumor tissue. Doxorubicin (DOX) encapsulated in Z-MSN was not significantly released in physiological conditions (pH 7.4), whereas the release rate of DOX remarkably increased in mildly acidic conditions through disintegration of the gatekeeper. The antitumor efficacy of DOX-loaded Z-MSN (DOX-Z-MSN) was evaluated after their systemic administration to tumor-bearing mice. Compared to free DOX and DOX-loaded MSN without the gatekeeper, DOX-Z-MSN exhibited much higher antitumor efficacy in vivo. Overall, these results demonstrated that the hydrophilic negative surface of Z-MSN, with their closed gate, allowed for their effective accumulation in tumor tissue after systemic administration, and that their charge-swapping and gate-opening in the tumor environment enhanced their cellular uptake and drug release rate simultaneously, implying a highly promising potential for development of Z-MSN as a drug carrier for cancer therapy. STATEMENT OF SIGNIFICANCE: In an attempt to address the issues of enhanced cellular uptake and site-specific drug release of nanoparticles, we herein report on zwitterionic MSN (Z-MSN) with a pH-responsive gatekeeper which can be internalized into cancer cells via switching their surface charge from negative, in physiological conditions, to positive, in the tumor microenvironment. We hypothesized that the hydrophilic negative surface of Z-MSN with a closed gate allows for their accumulation into tumor tissue after systemic administration, whereas their charge-swapping and gate-opening in the tumor environment enhance cellular uptake and drug release rate simultaneously. Overall, Z-MSN constitute a promising drug delivery carrier for cancer therapy.

Recent developments in hyaluronic acid-based nanomedicine for targeted cancer treatment.

INTRODUCTION: Hyaluronic acid (HA) has emerged as a promising applicant for the tumor-targeted delivery of various therapeutic agents. Because of its biocompatibility, biodegradability and receptor-binding properties, HA has been extensively investigated as the drug delivery carrier. In this review, recent advances in HA-based nanomedicines are discussed. AREAS COVERED: This review focuses on HA-based nanomedicines for the diagnosis and treatment of cancer. In particular, recent advances in HA-drug conjugates and HA-based nanoparticles for small molecular drug delivery are discussed. The bioreducible HA conjugates for small interfering ribonucleic acid delivery have been also discussed. EXPERT OPINION: To develop a successful HA-based nanomedicine, it has to be prepared without significant deterioration of intrinsic property of HA. The chemical modification of HA with drugs or hydrophobic moieties may reduce the binding affinity of HA to the receptors. In addition, since the HA-based nanomedicines tend to accumulate in the liver after their systemic administration, new strategies to overcome this issue have to be developed.

A pH-responsive carboxymethyl dextran-based conjugate as a carrier of docetaxel for cancer therapy.

Although docetaxel is available for the treatment of various cancers, its clinical applications are limited by its poor water solubility and toxicity to normal cells, resulting in severe adverse effects. In this study, we synthesized a polymeric conjugate with an acid-labile ester linkage, consisting of carboxymethyl dextran (CMD) and docetaxel (DTX), as a potential anticancer drug delivery system. The conjugate exhibited sustained release of DTX in physiological buffer (pH 7.4), whereas its release rate increased remarkably under mildly acidic conditions (pH < 6.5), mimicking the intracellular environment. Cytotoxicity tests conducted in vitro demonstrated that the conjugate exhibited much higher toxicity to cancer cells under mildly acidic conditions than at physiological buffer (pH 7.4). These results implied that the ester linkage in the conjugate allowed for selective release of biologically active DTX under mildly acidic conditions. The in vivo biodistribution of a Cy5.5-labeled conjugate was observed using the noninvasive optical imaging technique after its systemic administration into tumor-bearing mice. The conjugate was effectively accumulated into the tumor site, which may have been because of an enhanced permeability and retention effect. In addition, in vivo antitumor efficacy of the conjugate was significantly higher than that of free DTX. Overall, the CMD-based conjugate might have promising potential as a carrier of DTX for cancer therapy.