Use of Antipsychotic Medications and Cholinesterase Inhibitors and the Risk of Falls and Fractures: self-controlled case series

Objective: To evaluate the association between the use of antipsychotic medications and cholinesterase inhibitors, and the risk of falls and fractures in elderly patients with major neurocognitive disorders. / Design: Self-controlled case series / Setting: Taiwan’s National Health Insurance Database / Participants: 15,278 patients who were aged 65 or older, were newly prescribed antipsychotic medications and cholinesterase inhibitors, and suffered an incident fall or fracture between 2006 and 2017. Prescription records of cholinesterase inhibitors were used to confirm the diagnosis of major neurocognitive disorders since all use of cholinesterase inhibitors was subject to review by experts based on the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition and patients’ scores of Mini-Mental State Examination. We excluded those with schizophrenia and bipolar disorder before the first prescription of cholinesterase inhibitors to ensure that antipsychotic medications were used for neuropsychiatric symptoms of major neurocognitive disorders. / Main outcome measures: We used conditional Poisson regression to derive the incidence rate ratio and the 95% confidence interval for evaluating the association between the risk of falls and fractures and different exposure periods, including cholinesterase inhibitors alone, antipsychotic medications alone, and combination, as compared with the non-exposure period for the same individual. Moreover, we defined a 14-day pre-exposure period before study drug initiation over concerns about confounding by indication. / Results: Compared with the non-exposure period (incidence rate per 100 person-years; 95% confidence interval: 8.30; 8.14 to 8.46), the highest risk of falls and fractures occurred during the pre-exposure period (52.35; 48.46 to 56.47), followed by combination (10.55; 9.98 to 11.14), antipsychotic medications alone (10.34; 9.80 to 10.89), and cholinesterase inhibitors alone (9.41; 8.98 to 9.86). Conclusions: The incidence of falls and fractures was especially high in the pre-exposure period, suggesting that factors other than the study medications, such as underlying diseases, should be taken into consideration when evaluating the association between the risk of falls and fractures, and the use of cholinesterase inhibitors and antipsychotic medications. The exposure periods were also associated with a higher risk of falls and fractures, compared with the non-exposure period, although the magnitude was much lower than during the pre-exposure period. Prevention strategies and close monitoring of the risk of falls are still necessary until there is evidence that patients have regained a steady status

A correlation study between in-brace correction, compliance to spinal orthosis and health-related quality of life of patients with Adolescent Idiopathic Scoliosis

BACKGROUND: It has been proposed that in-brace correction is the best guideline for prediction of the results of brace treatment for patients with Adolescent Idiopathic Scoliosis (AIS). However, bracing may be a stressful experience for patients and bracing non-compliance could be psychologically related. The purpose of this study was to assess the correlation between brace compliance, in-brace correction and QoL of patients with AIS. METHODS: Fifty-five patients with a diagnosis of AIS were recruited. All were female and aged 10 years or above when a brace was prescribed, none had undergone prior treatment, and all had a Risser sign of 0–2 and a Cobb angle of 25-40°. The patients were examined in three consecutive visits with 4 to 6 months between each visit. The Chinese translated Trunk Appearance Perception Scale (TAPS), the Chinese translated Brace Questionnaires (BrQ) and the Chinese translated SRS-22 Questionnaires were used in the study. The in-brace Cobb angle, vertebral rotation and trunk listing were also measured. Patients’ compliance, in-brace correction and patients’ QoL were assessed. To identify the relationship among these three areas, logistic regression model and generalized linear model were used. RESULT: For the compliance measure, a significant difference (p = 0.008) was detected on TAPS mean score difference between Visit 1 and Visit 2 in the least compliant group (0–8 hours) and the most compliant group (17–23 hours). In addition, a significant difference (p = 0.000) was detected on BrQ mean score difference between Visit 2 and Visit 3 in the least compliant group (0–8 hours) and the most compliant group (17–23 hours). For the orthosis effectiveness measure, no significant difference was detected between the three groups of bracing hours (0–8 hours, 9–16 hours, 17–23 hours) on in-brace correction (below 40% and 40% or above). For the QoL measure, no significant difference was detected between the two different in-brace correction groups (below 40% and 40% or above) on QoL as reflected by the TAPS, BrQ and SRS-22r mean scores. CONCLUSION: The results showed a positive relationship between patients’ brace wear compliance and patients’ QoL. Poor compliance would cause a lower QoL

ERα inhibits epithelial-mesenchymal transition by suppressing Bmi1 in breast cancer

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ERα inhibits epithelial-mesenchymal transition by suppressing Bmi1 in breast cancer

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The Anti-Tumor Effects of M1 Macrophage-Loaded Poly (ethylene glycol) and Gelatin-Based Hydrogels on Hepatocellular Carcinoma

Background and Aims: Recently we reported that direct injection of M1 macrophages significantly caused tumor regression in vivo. Despite the promising result, a major limitation in translating this approach is the induction of acute inflammatory response. To improve the strategy, a biocompatible scaffold for cell presentation and support is essential to control cell fate. Here, we aimed to elucidate the anti-tumor effects of a poly(ethylene glycol) diacrylate (PEGdA) and thiolated gelatin poly(ethylene glycol) (Gel-PEG-Cys) cross-linked hydrogels capsulated with M1 macrophages in both in vitro and in vivo disease models. Methods: Hydrogels were made at 0.5% (w/v) Iragcure 2959 photoinitiator, 10% (w/v) PEGdA, and 10% (w/v) Gel-PEG-Cys. Monocytic THP-1 cells were loaded into hydrogels and differentiated into M1 macrophages with lipopolysaccharide (LPS) and interferon gamma (IFN-γ). The M1 hydrogels were then cocultivated with HCC cell-lines Hep3B and MHCC97L to investigate the anti-tumor capacities and the associated molecular profiles in vitro. A nude mice ectopic liver cancer model with dorsal window chamber (DWC) and a subcutaneous tumor model were both performed to validate the in vivo application of M1 hydrogels. Results: M1 hydrogels significantly decreased the viability of HCC cells (MHCC97L: -46%; Hep3B: -56.9%; P<0.05) compared to the control in vitro. In response to HCC cells, the hydrogel embedded M1 macrophages up-regulated nitrite and tumor necrosis factor alpha (TNF-α) activating caspase-3 induced apoptosis in the tumor cells. Increased tumor necrosis was observed in DWC filled with M1 hydrogels. In addition, mice treated with M1 hydrogels exhibited a significant 2.4-fold decrease in signal intensity of subcutaneous HCC tumor compared to control (P=0.036). Conclusion: M1 hydrogels induced apoptosis in HCC cells and tumor regression in vivo. Continuous development of the scaffold-based cancer immunotherapy may provide an alternative and innovative strategy against HCC.published_or_final_versio

The role of cancer nurses in cancer-related pain management in Europe

Cancer pain is a common symptom in patients with cancer and can largely affect their quality of life. Pain management is important to minimize the impact of pain on daily activities. Cancer nurses are significantly involved in all steps of pain management and contribute to the success of therapy through their knowledge and expertise. While they generally play an important role in the screening, assessment, diagnosis, treatment and follow-up of patients and their (pain) symptoms, this varies from country to country in Europe. An important aspect is their role in educating patients and their families about what pain is, what impact it can have, how it can be treated pharmacologically or non-pharmacologically and what effects or problems can occur during treatment. While there is a great discrepancy between education and training opportunities for cancer nurses in different European countries, there is a continued need for education and training in pain management. Cancer is increasingly becoming a chronic disease, and the management of pain in cancer survivors will be crucial to maintain an adequate quality of life. With this, the crucial role of cancer nurses is becoming even more important.info:eu-repo/semantics/publishedVersio

The clinical significance and potential therapeutic role of GPx3 in tumor recurrence after liver transplantation

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Clinical significance and therapeutic value of glutathione peroxidase 3 (GPx3) in hepatocellular carcinoma

AIMS: We aimed to investigate the clinical significance of GPx3 in hepatocellular carcinoma (HCC) and to characterize its tumor suppressive role. METHODS: HCC patients (113) who underwent hepatectomy were recruited to examine the clinical relevance of GPx3. The tumor suppressive role of GPx3 was studied by administration of recombinant GPx3 (rGPx3) or over-expression of GPx3 in HCC cells in vitro and in vivo. The therapeutic value of GPx3 for HCC was further investigated using human induced pluripotent stem cell derived mesenchymal stem cells (hiPSC-MSCs) as its delivery vehicle. RESULTS: Down-regulation of GPx3 significantly correlated with advanced tumor stage (P = 0.024), venous infiltration (P = 0.043) and poor overall survival (P = 0.007) after hepatectomy. Lower plasma GPx3 in HCC patients was significantly associated with larger tumor size (P = 0.011), more tumor nodules (P = 0.032) and higher recurrence (P = 0.016). Over-expression of GPx3 or administration of rGPx3 significantly inhibited proliferation and invasiveness of HCC cells in vitro and in vivo. Tumor suppressive activity of GPx3 was mediated through Erk-NFκB-SIP1 pathway. GPx3 could be delivered by hiPSC-MSCs into the tumor and exhibited tumor suppressive activity in vivo. CONCLUSIONS: GPx3 is a tumor suppressor gene in HCC and may possess prognostic and therapeutic value for HCC patients.published_or_final_versio

Elevated adipogenesis of marrow mesenchymal stem cells during early steroid-associated osteonecrosis development

<p>Abstract</p> <p>Background</p> <p>Increased bone marrow lipid deposition in steroid-associated osteonecrosis (ON) implies that abnormalities in fat metabolism play an important role in ON development. The increase in lipid deposition might be explained by elevated adipogenesis of marrow mesenchymal stem cells (MSCs). However, it remains unclear whether there is a close association between elevated adipogenesis and steroid-associated ON development.</p> <p>Objective</p> <p>The present study was designed to test the hypothesis that there might be a close association between elevated adipogenesis and steroid-associated ON development.</p> <p>Methods</p> <p>ON rabbit model was induced based on our established protocol. Dynamic-MRI was employed for local intra-osseous perfusion evaluation in bilateral femora. Two weeks after induction, bone marrow was harvested for evaluating the ability of adipogenic differentiation of marrow MSCs at both cellular and mRNA level involving adipogenesis-related gene peroxisome proliferator-activated receptor gamma2 (PPARγ2). The bilateral femora were dissected for examining marrow lipid deposition by quantifying fat cell number, fat cell size, lipid deposition area and ON lesions. For investigating association among adipogenesis, lipid deposition and perfusion function with regard to ON occurrence, the rabbits were divided into ON⁺(with at least one ON lesion) group and ON^-(without ON lesion) group. For investigating association among adipogenesis, lipid deposition and perfusion function with regard to ON extension, the ON⁺rabbits were further divided into sub-single-lesion group (SON group: with one ON lesion) and sub-multiple-lesion group (MON group: with more than one ON lesion).</p> <p>Results</p> <p>Local intra-osseous perfusion index was found lower in either ON⁺or MON group when compared to either ON^-or SON group, whereas the marrow fat cells number and area were much larger in either ON⁺or MON group as compared with ON^-and SON group. The adipogenic differentiation ability of MSCs and PPARγ2 expression in either ON⁺or MON group were elevated significantly as compared with either ON^-or SON group.</p> <p>Conclusion</p> <p>These findings support our hypothesis that there is a close association between elevated adipogenesis and steroid-associated osteonecrosis development.</p

CXCL10/CXCR3 signaling mobilized-regulatory T cells promote liver tumor recurrence after transplantation

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