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1.
J Clin Pharm Ther ; 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31670842

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Several Caucasian cohort studies have associated at least one loss-of-function CYP2C19 on Clopidogrel (LoF-Clopidogrel) with major adverse cardiovascular events (MACE), and only a couple have used Clinical Pharmacogenetics Implementation Consortium (CPIC® ) phenotype grouping to study the associations. We primarily aimed to study the impact of use of platelet reactivity testing to escalate antiplatelet therapy and secondarily to study the association of CPIC phenotype with MACE outcomes in South-East Asian Acute Coronary Syndrome (ACS) subjects. METHOD: A retrospective genotype study was performed on 238 percutaneous coronary intervention subjects, originally planned for escalation of antiplatelets using platelet reactivity testing. RESULTS AND DISCUSSION: There was no difference in MACE between the switched and unswitched groups; however, 'all bleeds' and 'clinically significant bleeds' (CSB) were statistically higher in the patients who were switched to prasugrel. The subgroup of patients who remained on clopidogrel (n = 199) were analysed using phenotype categories and MACE. Eleven percent (11.4%) of CYP2C19 poor metabolizers (PM) suffered MACE, compared with 1.3% of extensive metabolizers (EM). LoF-Clopidogrel patients are significantly more likely to experience MACE compared with non-LoF subjects (8.0% vs 5.4%, P: .041). WHAT IS NEW AND CONCLUSION: In our multivariate analysis, LoF-Clopidogrel, malay ethnicity, diabetics and use of proton pump inhibitors were independent predictors of MACE. There were numerically more bleeds in LoF subjects who were on prasugrel compared with Clopidogrel (23.5% vs 11%, P = .082). Our data corroborate with current findings on platelet reactivity testing, suggesting that the assay would not be sensitive enough to pick up sufficient 'at-risk' subjects as compared to the use of CYP2C19 genotyping.

2.
Sci Data ; 6(1): 280, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31767854

RESUMO

Complete genomes of xenobiotic-degrading microorganisms provide valuable resources for researchers to understand molecular mechanisms involved in bioremediation. Despite the well-known ability of Sphingomonas paucimobilis to degrade persistent xenobiotic compounds, a complete genome sequencing is lacking for this organism. In line with this, we report the first complete genome sequence of Sphingomonas paucimobilis (strain AIMST S2), an organophosphate and hydrocarbon-degrading bacterium isolated from oil-polluted soil at Kedah, Malaysia. The genome was derived from a hybrid assembly of short and long reads generated by Illumina HiSeq and MinION, respectively. The assembly resulted in a single contig of 4,005,505 bases which consisted of 3,612 CDS and 56 tRNAs. An array of genes involved in xenobiotic degradation and plant-growth promoters were identified, suggesting its' potential role as an effective microorganism in bioremediation and agriculture. Having reported the first complete genome of the species, this study will serve as a stepping stone for comparative genome analysis of Sphingomonas strains and other xenobiotic-degrading microorganisms as well as gene expression studies in organophosphate biodegradation.

3.
Org Lett ; 21(20): 8339-8343, 2019 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-31566385

RESUMO

We report a phosphine-mediated direct ß-acylation of α,ß-unsaturated 1,3-diketones with acyl chlorides and a base. Functionalized furanones were also prepared by the reaction of cinnamic acid and acyl chloride according to our protocol via ß-acylation. Our studies revealed that α,ß-unsaturated 1,3-diketones with an electron-donating group at the second position favor the formation of ß-acylated products, whereas those with oxygen, such as anhydrides, favor furanones via an unprecedented C-acylation/cyclization sequence.

4.
Educ Prim Care ; : 1-7, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31581895

RESUMO

The importance of Social Prescribing (SP) has been highlighted in the National Health Service (NHS) Long-Term Plan. SP is enabling healthcare professionals to refer patients to a link worker, to co-design a non-clinical social prescription to improve their health and well-being. Our aim was to explore perceptions, understanding, and awareness of SP amongst United Kingdom (UK) medical students. Views were collected using pre- and post-session surveys around teaching sessions in 27 UK medical schools as part of NHS England's National SP Student Champion Scheme. Pre-session surveys suggested 93% (n = 848) of respondents had not heard of the concept of SP before the session. Post-session surveys highlighted that 98% (n = 895) regarded the concept as useful and relevant to their future careers. Findings show a lack of awareness regarding Social Prescribing (SP) amongst UK medical students. New strategies are needed to ensure the doctors of tomorrow are equipped with the necessary tools to achieve the recent outcomes for graduates and implement plans for the NHS and general practice which highlight the importance of personalised care. We believe general practice can play an integral role in shaping values and beliefs amongst tomorrow's doctors through formal education and mentoring.

5.
Am J Physiol Gastrointest Liver Physiol ; 317(5): G625-G639, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31545917

RESUMO

Dissemination of primary tumors to distant anatomical sites has a substantial negative impact on patient prognosis. The liver is a common site for metastases from colorectal cancer, and patients with hepatic metastases have generally much shorter survival, raising a need to develop and implement novel strategies for targeting metastatic disease. The extracellular matrix (ECM) is a meshwork of highly crosslinked, insoluble high-molecular-mass proteins maintaining tissue integrity and establishing cell-cell interactions. Emerging evidence identifies the importance of the ECM in cancer cell migration, invasion, intravasation, and metastasis. Here, we isolated the ECM from MC38 mouse liver metastases using our optimized method of mild detergent solubilization followed by biochemical enrichment. The matrices were subjected to label-free quantitative mass spectrometry analysis, revealing proteins highly abundant in the metastatic matrisome. The resulting list of proteins upregulated in the ECM significantly predicted survival in patients with colorectal cancer but not other cancers with strong involvement of the ECM component. One of the proteins upregulated in liver metastatic ECM, annexin A1, was not previously studied in the context of cancer-associated matrisome. Here, we show that annexin A1 was markedly upregulated in colon cancer cell lines compared with cancer cells of other origin and also over-represented in human primary colorectal lesions, as well as hepatic metastases, compared with their adjacent healthy tissue counterparts. In conclusion, our study provides a comprehensive ECM characterization of MC38 experimental liver metastases and proposes annexin A1 as a putative target for this disease.NEW & NOTEWORTHY Here, the authors provide an extensive proteomics characterization of murine colorectal cancer liver metastasis matrisome (the ensemble of all extracellular matrix molecules). The findings presented in this study may enable identification of therapeutic targets or biomarkers of hepatic metastases.

6.
Ann Rheum Dis ; 2019 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-31537547

RESUMO

OBJECTIVES: Open-labelled clinical trials suggested that low-dose IL-2 might be effective in treatment of systemic lupus erythematosus (SLE). A double-blind and placebo-controlled trial is required to formally evaluate the safety and efficacy of low-dose IL-2 therapy. METHODS: A randomised, double-blind and placebo-controlled clinical trial was designed to treat 60 patients with active SLE. These patients received either IL-2 (n=30) or placebo (n=30) with standard treatment for 12 weeks, and were followed up for additional 12 weeks. IL-2 at a dose of 1 million IU or placebo was administered subcutaneously every other day for 2 weeks and followed by a 2-week break as one treatment cycle. The primary endpoint was the SLE Responder Index-4 (SRI-4) at week 12. The secondary endpoints were other clinical responses, safety and dynamics of immune cell subsets. RESULTS: At week 12, the SRI-4 response rates were 55.17% and 30.00% for IL-2 and placebo, respectively (p=0.052). At week 24, the SRI-4 response rate of IL-2 group was 65.52%, compared with 36.67% of the placebo group (p=0.027). The primary endpoint was not met at week 12. Low-dose IL-2 treatment resulted in 53.85% (7/13) complete remission in patients with lupus nephritis, compared with 16.67% (2/12) in the placebo group (p=0.036). No serious infection was observed in the IL-2 group, but two in placebo group. Besides expansion of regulatory T cells, low-dose IL-2 may also sustain cellular immunity with enhanced natural killer cells. CONCLUSIONS: Low-dose IL-2 might be effective and tolerated in treatment of SLE. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registries (NCT02465580 and NCT02932137).

7.
Artigo em Inglês | MEDLINE | ID: mdl-31518489

RESUMO

Inhibitors targeting the mitogen-activated protein kinase (MAPK) pathway and immune checkpoint molecules have dramatically improved the survival of patients with BRAFV600 -mutant melanoma. For BRAF/RAS wild-type (WT) melanoma patients, however, immune checkpoint inhibitors remain the only effective therapeutic option with 40% of patients responding to PD-1 inhibition. In the present study, a large panel of 10 BRAFV600 -mutant and 13 BRAF/RAS WT melanoma cell lines was analyzed to examine MAPK dependency and explore the potential utility of MAPK inhibitors in this melanoma subtype. We now show that the majority of BRAF/RAS WT melanoma cell lines (8/13) display some degree of sensitivity to trametinib treatment and resistance to trametinib in this melanoma subtype is associated with, but not mediated by NF1 suppression. Although knockdown of NF1 stimulates RAS and CRAF activity, the activation of CRAF by NF1 knockdown is limited by ERK-dependent feedback in BRAF-mutant cells, but not in BRAF/RAS WT melanoma cells. Thus, NF1 is not a dominant regulator of MAPK signaling in BRAF/RAS WT melanoma, and co-targeting multiple MAP kinase nodes provides a therapeutic opportunity for this melanoma subtype.

9.
J Org Chem ; 84(19): 12259-12267, 2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31315398

RESUMO

A general one-step synthesis of symmetrical or unsymmetrical 1,4-di(organo)fullerenes from organo(hydro)fullerenes (RC60H) is realized by direct oxidative arylation. The new combination of catalytic trifluoromethanesulfonic acid (TfOH) and stoichiometric o-chloranil is the first to be used to directly generate an R-C60+ intermediate from common RC60H. Unexpectedly, the in situ generated R-C60+ intermediate is shown to be quite stable in whole 13C NMR spectroscopy characterization in the absence of cation quenching reagents. Because the direct oxidation of common RC60H to form the corresponding R-C60+ has never been realized, the present combination of TfOH and o-chloranil solves the challenges associated with the formation of stable RC60+ cations from common RC60H without any coordination of an R group.

10.
PLoS Negl Trop Dis ; 13(7): e0007555, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31356617

RESUMO

Targeted environmental and ecosystem management remain crucial in control of dengue. However, providing detailed environmental information on a large scale to effectively target dengue control efforts remains a challenge. An important piece of such information is the extent of the presence of potential dengue vector breeding sites, which consist primarily of open containers such as ceramic jars, buckets, old tires, and flowerpots. In this paper we present the design and implementation of a pipeline to detect outdoor open containers which constitute potential dengue vector breeding sites from geotagged images and to create highly detailed container density maps at unprecedented scale. We implement the approach using Google Street View images which have the advantage of broad coverage and of often being two to three years old which allows correlation analyses of container counts against historical data from manual surveys. Containers comprising eight of the most common breeding sites are detected in the images using convolutional neural network transfer learning. Over a test set of images the object recognition algorithm has an accuracy of 0.91 in terms of F-score. Container density counts are generated and displayed on a decision support dashboard. Analyses of the approach are carried out over three provinces in Thailand. The container counts obtained agree well with container counts from available manual surveys. Multi-variate linear regression relating densities of the eight container types to larval survey data shows good prediction of larval index values with an R-squared of 0.674. To delineate conditions under which the container density counts are indicative of larval counts, a number of factors affecting correlation with larval survey data are analyzed. We conclude that creation of container density maps from geotagged images is a promising approach to providing detailed risk maps at large scale.

11.
Proc Natl Acad Sci U S A ; 116(32): 15836-15841, 2019 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-31324742

RESUMO

In this report we examine a family of trinuclear iron complexes by multiple-wavelength, anomalous diffraction (MAD) to explore the redox load distribution within cluster materials by the free refinement of atomic scattering factors. Several effects were explored that can impact atomic scattering factors within clusters, including 1) metal atom primary coordination sphere, 2) M-M bonding, and 3) redox delocalization in formally mixed-valent species. Complexes were investigated which vary from highly symmetric to fully asymmetric by 57Fe Mössbauer and X-ray diffraction to explore the relationship between MAD-derived data and the data available from these widely used characterization techniques. The compounds examined include the all-ferrous clusters [ n Bu4N][(tbsL)Fe3(µ3-Cl)] (1) ([tbsL]6- = [1,3,5-C6H9(NC6H4-o-NSi t BuMe2)3]6-]), (tbsL)Fe3(py) (2), [K(C222)]2[(tbsL)Fe3(µ3-NPh)] (4) (C222 = 2,2,2-cryptand), and the mixed-valent (tbsL)Fe3(µ3-NPh) (3). Redox delocalization in mixed-valent 3 was explored with cyclic voltammetry (CV), zero-field 57Fe Mössbauer, near-infrared (NIR) spectroscopy, and X-ray crystallography techniques. We find that the MAD results show an excellent correspondence to 57Fe Mössbauer data; yet also can distinguish between subtle changes in local coordination geometries where Mössbauer cannot. Differences within aggregate oxidation levels are evident by systematic shifts of scattering factor envelopes to increasingly higher energies. However, distinguishing local oxidation levels in iso- or mixed-valent materials can be dramatically obscured by the degree of covalent intracore bonding. MAD-derived atomic scattering factor data emphasize in-edge features that are often difficult to analyze by X-ray absorption near edge spectroscopy (XANES). Thus, relative oxidation levels within the cluster were most reliably ascertained from comparing the entire envelope of the atomic scattering factor data.

13.
BMC Cancer ; 19(1): 538, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31164099

RESUMO

BACKGROUND: Despite recent advances in the treatments of hepatocellular carcinoma (HCC), the prognosis of HCC patients remains controversial. The purpose of this study was to investigate the prognostic performance of pretreatment albumin to C-reactive protein ratio (ACR) in patients with HCC. METHODS: This study included 409 initially diagnosed HCC patients retrospectively. The optimal cut-off points for distinguishing high and low ACR value was determined by the X-tile software. The chi-squared test was used for comparing the baseline clinicopathologic parameters in different groups and subgroups. The Cox regression with log-rank tests was used to analyze OS and DFS, and Kaplan-Meier curves was used to estimate the prognosis of HCC patients. RESULTS: Patients with lower ACR were significantly correlated with advanced clinical parameters, using a cut-off points of 5.4 (high ACR, n = 236 vs. low ACR, n = 173). Multivariate analysis demonstrated that ACR was associated with OS (HR = 0.544, 95% CI: 0.385-0.769, p = 0.001), with DFS (HR = 0.550, 95% CI: 0.392-0.772, p = 0.001). Treatment exposure (HR = 2.191; 95% CI: 1.533-3.132; p <  0.001), tumor size (HR = 1.973; 95% CI: 1.230-3.164; p = 0.005), serum AFP level (HR = 1.752; 95% CI: 1.277-2.403; p = 0.001), and TNM stage (HR = 0.470; 95% CI: 0.319-2.504; p <  0.001), were independent factors for OS in HCC patients. Treatment exposure (HR = 2.244; 95% CI: 1.590-3.166; p <  0.001), TNM stage (HR = 2.075; 95% CI: 1.436-3.000; p <  0.001), serum AFP level (HR = 1.819; 95% CI: 1.340-2.469; p = 0.001), tumor size (HR = 1.730; 95% CI: 1.113-2.689; p = 0.015), and ACR (HR = 0.550; 95% CI: 0.392-0.772; p = 0.001) were independent factors for DFS in HCC patients. CONCLUSIONS: Pretreatment ACR is a convenient and useful parameter for HCC patients predicting OS and DFS. Lower ACR was associated with advanced TNM stage, larger tumor size, and a high concentration of AFP. These results may help to design strategies to personalize management approaches among HCC patients.

14.
Int J Mol Sci ; 20(10)2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31100908

RESUMO

Cardiovascular diseases (CVDs) have been considered the most predominant cause of death and one of the most critical public health issues worldwide. In the past two decades, cardiovascular (CV) mortality has declined in high-income countries owing to preventive measures that resulted in the reduced burden of coronary artery disease (CAD) and heart failure (HF). In spite of these promising results, CVDs are responsible for ~17 million deaths per year globally with ~25% of these attributable to sudden cardiac death (SCD). Pre-clinical data demonstrated that renal denervation (RDN) decreases sympathetic activation as evaluated by decreased renal catecholamine concentrations. RDN is successful in reducing ventricular arrhythmias (VAs) triggering and its outcome was not found inferior to metoprolol in rat myocardial infarction model. Registry clinical data also suggest an advantageous effect of RDN to prevent VAs in HF patients and electrical storm. An in-depth investigation of how RDN, a minimally invasive and safe method, reduces the burden of HF is urgently needed. Myocardial systolic dysfunction is correlated to neuro-hormonal overactivity as a compensatory mechanism to keep cardiac output in the face of declining cardiac function. Sympathetic nervous system (SNS) overactivity is supported by a rise in plasma noradrenaline (NA) and adrenaline levels, raised central sympathetic outflow, and increased organ-specific spillover of NA into plasma. Cardiac NA spillover in untreated HF individuals can reach ~50-fold higher levels compared to those of healthy individuals under maximal exercise conditions. Increased sympathetic outflow to the renal vascular bed can contribute to the anomalies of renal function commonly associated with HF and feed into a vicious cycle of elevated BP, the progression of renal disease and worsening HF. Increased sympathetic activity, amongst other factors, contribute to the progress of cardiac arrhythmias, which can lead to SCD due to sustained ventricular tachycardia. Targeted therapies to avoid these detrimental consequences comprise antiarrhythmic drugs, surgical resection, endocardial catheter ablation and use of the implantable electronic cardiac devices. Analogous NA agents have been reported for single photon-emission-computed-tomography (SPECT) scans usage, specially the 123I-metaiodobenzylguanidine (123I-MIBG). Currently, HF prognosis assessment has been improved by this tool. Nevertheless, this radiotracer is costly, which makes the use of this diagnostic method limited. Comparatively, positron-emission-tomography (PET) overshadows SPECT imaging, because of its increased spatial definition and broader reckonable methodologies. Numerous ANS radiotracers have been created for cardiac PET imaging. However, so far, [11C]-meta-hydroxyephedrine (HED) has been the most significant PET radiotracer used in the clinical scenario. Growing data has shown the usefulness of [11C]-HED in important clinical situations, such as predicting lethal arrhythmias, SCD, and all-cause of mortality in reduced ejection fraction HF patients. In this article, we discussed the role and relevance of novel tools targeting the SNS, such as the [11C]-HED PET cardiac imaging and RDN to manage patients under of SCD risk.


Assuntos
Morte Súbita Cardíaca/etiologia , Insuficiência Cardíaca/complicações , Sistema Nervoso Simpático/efeitos dos fármacos , 3-Iodobenzilguanidina , Animais , Arritmias Cardíacas , Catecolaminas/urina , Modelos Animais de Doenças , Efedrina/análogos & derivados , Coração , Humanos , Infarto do Miocárdio , Miocárdio , Tomografia por Emissão de Pósitrons , Taquicardia Ventricular , Tomografia Computadorizada de Emissão de Fóton Único , Disfunção Ventricular Esquerda
15.
Perspect Health Inf Manag ; 16(Spring): 1a, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31019433

RESUMO

Purpose: Because user acceptance and resistance to the use of health information technology (HIT) affects system utilization and previous studies in this area have typically excluded pharmacists, this study specifically addresses the response of institutional pharmacists to HIT. Methods: A survey investigating pharmacists' responses to electronic medical record (EMR) system use was developed using questions modified from previously validated research. The survey was distributed electronically to the mailing list for pharmacy preceptors for the University of Tennessee College of Pharmacy. Descriptive statistics and univariate and multivariate analyses were used to analyze the collected data based on a previously validated dual-factor model. Results: Of the 96 responses from institutional pharmacists, 64 responses (66.7 percent) were complete and usable. Of the acceptance and resistance constructs evaluated, only attitude and perceived behavior control were found to be significantly associated with acceptance of use (p = .036 and p = .025, respectively), and only transition cost was found to be significantly associated with resistance to use (p = .018). System vendor and interface integration were also significantly associated with acceptance of use. These findings suggest that attitude, perceived behavior control, and transition costs may have the most impact on pharmacists' responses to the use of EMR systems. Conclusion: It is reasonable for hospitals to focus efforts on specific factors influencing acceptance of and resistance to EMR use and, before a system is selected, to consider the effects of vendor selection and level of interface integration on acceptance of use.

16.
Ann Rheum Dis ; 78(6): 773-780, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30936065

RESUMO

OBJECTIVE: The strong genetic contribution of the major histocompatibility complex (MHC) region to rheumatoid arthritis (RA) has been generally attributed to human leukocyte antigen (HLA)-DRB1. However, due to the high polymorphisms and linkage disequilibrium within MHC, it is difficult to define novel and/or independent genetic risks using conventional HLA genotyping or chip-based microarray technology. This study aimed to identify novel RA risk variants by performing deep sequencing for MHC. METHODS: We first conducted target sequencing for the entire MHC region in 357 anticitrullinated protein antibodies (ACPA)-positive patients with RA and 1001 healthy controls, and then performed HLA typing in an independent case-control cohort consisting of 1415 samples for validation. All study subjects were Han Chinese. Genetic associations for RA susceptibility and severity were analysed. Comparative modelling was constructed to predict potential functions for the newly discovered RA association variants. RESULTS: HLA-DQα1:160D conferred the strongest and independent susceptibility to ACPA-positive RA (p=6.16×10-36, OR=2.29). DRß1:37N had an independent protective effect (p=5.81×10-16, OR=0.49). As predicted by comparative modelling, the negatively charged DQα1:160D stabilises the dimer of dimers, thus may lead to an increased T cell activation. The negatively charged DRß1:37N encoding alleles preferentially bind with epitope P9 arginine, thus may result in a decreased RA susceptibility. CONCLUSIONS: We provide the first evidence that HLA-DQα1:160D, instead of HLA-DRB1*0405, is the strongest and independent genetic risk for ACPA-positive RA in Han Chinese. Our study also illustrates the value of deep sequencing for fine-mapping disease risk variants in the MHC region.

17.
J Exp Bot ; 70(16): 4237-4250, 2019 08 19.
Artigo em Inglês | MEDLINE | ID: mdl-30868163

RESUMO

The sulfur metabolism pathway in plants produces a variety of compounds that are central to the acclimation response to oxidative stresses such as drought and high light. Primary sulfur assimilation provides the amino acid cysteine, which is utilized in protein synthesis and as a precursor for the cellular redox buffer glutathione. In contrast, the secondary sulfur metabolism pathway produces sulfated compounds such as glucosinolates and sulfated peptides, as well as a corresponding by-product 3'-phosphoadenosine 5'-phosphate (PAP). Emerging evidence over the past decade has shown that secondary sulfur metabolism also has a crucial engagement during oxidative stress. This occurs across various cellular, tissue, and organismal levels including chloroplast-to-nucleus retrograde signalling events mediated by PAP, modulation of hormonal signalling by sulfated compounds and PAP, control of physiological responses such as stomatal closure, and potential regulation of plant growth. In this review, we examine the contribution of the different components of plant secondary metabolism to oxidative stress homeostasis, and how this pathway is metabolically regulated. We further outline the key outstanding questions in the field that are necessary to understand how and why this 'specialized' metabolic pathway plays significant roles in plant oxidative stress tolerance.

19.
BMC Health Serv Res ; 19(1): 177, 2019 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-30890134

RESUMO

BACKGROUND: To cope with rising demand for healthcare services in Singapore, Regional Health Systems (RHS) comprising of health and social care providers across care settings were set up to integrate service delivery. Tasked with providing care for the western region, in 2012, the National University Health System (NUHS) - RHS developed a transitional care program for elderly patients with complex healthcare needs who consumed high levels of hospital resources. Through needs assessment, development of personalized care plans and care coordination, the program aimed to: (i) improve quality of care, (ii) reduce hospital utilization, and (iii) reduce healthcare-related costs. In this study, recognizing the need for process evaluation in conjunction with outcome evaluation, we aim to evaluate the implementation fidelity of the NUHS-RHS transitional care program to explain the outcomes of the program and to inform further development of (similar) programs. METHODS: Guided by the modified version of the Conceptual Framework for Implementation Fidelity (CFIF), adherence and moderating factors influencing implementation were assessed using non-participatory observations, reviews of medical records and program databases. RESULTS: Most (10 out of 14) components of the program were found to be implemented with low or moderate level of fidelity. The frequency or duration of the program components were observed to vary based on the needs of users, availability of care coordinators (CC) and their confidence. Variation in fidelity was influenced predominantly by: (1) complexity of the program, (2) extent of facilitation through guiding protocols, (3) facilitation of program implementation through CCs' level of training and confidence, (4) evolving healthcare participant responsiveness, and (5) the context of suboptimal capability among community providers. CONCLUSION: This is the first study to assess the context-specific implementation process of a transitional care program in the context of Southeast Asia. It provides important insights to facilitate further development and scaling up of transitional care programs within the NUHS-RHS and beyond. Our findings highlight the need for greater focus on engaging both healthcare providers and users, training CCs to equip them with the relevant skills required for their jobs, and building the capability of the community providers to implement such programs.


Assuntos
Assistência à Saúde/organização & administração , Cuidado Transicional/organização & administração , Idoso , Programas Governamentais , Pessoal de Saúde , Humanos , Determinação de Necessidades de Cuidados de Saúde , Administração dos Cuidados ao Paciente , Singapura
20.
Angew Chem Int Ed Engl ; 58(17): 5687-5691, 2019 Apr 16.
Artigo em Inglês | MEDLINE | ID: mdl-30828957

RESUMO

The trichromium cluster (tbs L)Cr3 (thf) ([tbs L]6- =[1,3,5-C6 H9 (NC6 H4 -o-NSit BuMe2 )3 ]6- ) exhibits steric- and solvation-controlled reactivity with organic azides to form three distinct products: reaction of (tbs L)Cr3 (thf) with benzyl azide forms a symmetrized bridging imido complex (tbs L)Cr3 (µ3 -NBn); reaction with mesityl azide in benzene affords a terminally bound imido complex (tbs L)Cr3 (µ1 -NMes); whereas the reaction with mesityl azide in THF leads to terminal N-atom excision from the azide to yield the nitride complex (tbs L)Cr3 (µ3 -N). The reactivity of this complex demonstrates the ability of the cluster-templating ligand to produce a well-defined polynuclear transition metal cluster that can access distinct single-site and cooperative reactivity controlled by either substrate steric demands or reaction media.

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