Defining the characteristics of intermediate care models including transitional care: an international Delphi study.

BACKGROUND: Although there is growing utilisation of intermediate care to improve the health and well-being of older adults with complex care needs, there is no international agreement on how it is defined, limiting comparability between studies and reducing the ability to scale effective interventions. AIM: To identify and define the characteristics of intermediate care models. METHODS: A scoping review, a modified two-round electronic Delphi study involving 27 multi-professional experts from 13 countries, and a virtual consensus meeting were conducted. RESULTS: Sixty-six records were included in the scoping review, which identified four main themes: transitions, components, benefits and interchangeability. These formed the basis of the first round of the Delphi survey. After Round 2, 16 statements were agreed, refined and collapsed further. Consensus was established for 10 statements addressing the definitions, purpose, target populations, approach to care and organisation of intermediate care models. DISCUSSION: There was agreement that intermediate care represents time-limited services which ensure continuity and quality of care, promote recovery, restore independence and confidence at the interface between home and acute services, with transitional care representing a subset of intermediate care. Models are best delivered by an interdisciplinary team within an integrated health and social care system where a single contact point optimises service access, communication and coordination. CONCLUSIONS: This study identified key defining features of intermediate care to improve understanding and to support comparisons between models and studies evaluating them. More research is required to develop operational definitions for use in different healthcare systems.

Nicotinamide Riboside Augments the Aged Human Skeletal Muscle NAD+ Metabolome and Induces Transcriptomic and Anti-inflammatory Signatures.

Nicotinamide adenine dinucleotide (NAD+) is modulated by conditions of metabolic stress and has been reported to decline with aging in preclinical models, but human data are sparse. Nicotinamide riboside (NR) supplementation ameliorates metabolic dysfunction in rodents. We aimed to establish whether oral NR supplementation in aged participants can increase the skeletal muscle NAD+ metabolome and if it can alter muscle mitochondrial bioenergetics. We supplemented 12 aged men with 1 g NR per day for 21 days in a placebo-controlled, randomized, double-blind, crossover trial. Targeted metabolomics showed that NR elevated the muscle NAD+ metabolome, evident by increased nicotinic acid adenine dinucleotide and nicotinamide clearance products. Muscle RNA sequencing revealed NR-mediated downregulation of energy metabolism and mitochondria pathways, without altering mitochondrial bioenergetics. NR also depressed levels of circulating inflammatory cytokines. Our data establish that oral NR is available to aged human muscle and identify anti-inflammatory effects of NR.

MRS water resonance frequency in childhood brain tumours: a novel potential biomarker of temperature and tumour environment.

(1)H MRS thermometry has been investigated for brain trauma and hypothermia monitoring applications but has not been explored in brain tumours. The proton resonance frequency (PRF) of water is dependent on temperature but is also influenced by microenvironment factors, such as fast proton exchange with macromolecules, ionic concentration and magnetic susceptibility. (1)H MRS has been utilized for brain tumour diagnostic and prognostic purposes in children; however, the water PRF measure may provide complementary information to further improve characterization. Water PRF values were investigated from a repository of MRS data acquired from childhood brain tumours and children with apparently normal brains. The cohort consisted of histologically proven glioma (22), medulloblastoma (19) and control groups (28, MRS in both the basal ganglia and parietal white matter regions). All data were acquired at 1.5 T using a short TE (30 ms) single voxel spectroscopy (PRESS) protocol. Water PRF values were calculated using methyl creatine and total choline. Spectral peak amplitude weighted averaging was used to improve the accuracy of the measurements. Mean PRF values were significantly larger for medulloblastoma compared with glioma, with a difference in the means of 0.0147 ppm (p < 0.05), while the mean PRF for glioma was significantly lower than for the healthy cohort, with a difference in the means of 0.0061 ppm (p < 0.05). This would suggest the apparent temperature of the glioma group was ~1.5 °C higher than the medulloblastomas and ~0.7 °C higher than a healthy brain. However, the PRF shift may not reflect a change in temperature, given that alterations in protein content, microstructure and ionic concentration contribute to PRF shifts. Measurement of these effects could also be used as a supplementary biomarker, and further investigation is required. This study has shown that the water PRF value has the potential to be used for characterizing childhood brain tumours, which has not been reported previously.

Platelet nitric oxide and superoxide release during the development of nitrate tolerance: effect of supplemental ascorbate.

BACKGROUND: The therapeutic benefits that accompany the continuous administration of organic nitrates are attenuated by the development of tolerance to the compounds. Altered superoxide production and NO bioavailability have been implicated in contributing to the development of tolerance, an effect that may be ameliorated by the administration of antioxidants. METHODS AND RESULTS: We studied the effect of 3 days of continuous transdermal administration of nitroglycerin (NTG) (10 mg/24 hours) on platelet free radical (NO and superoxide anion [O2*-] activity) with and without coadministration of supplemental ascorbate (2.4 g/24 hours). NAD(P)H oxidase activity, nitric oxide synthase (NOS) activity, and cyclic guanosine monophosphate (cGMP) content were also assessed. Radial artery pressure pulse waveforms were used to track the hemodynamic actions of NTG. Three days of NTG/placebo was associated with a significant increase in platelet NO and O2*- production from 1.0+/-1.17 to 2.52+/-0.88 pmol/10(8) platelets and 13.2+/-4.8 to 72.5+/-34.4 pmol/10(8) platelets, respectively (P<0.01 for both). These changes were accompanied by increased platelet NADH oxidase activity from 47.9+/-11.0 to 65.3+/-13.6 pmol O2*- min/mg protein and cGMP content from 0.60+/-0.10 to 0.89+/-0.16 pmol/10(9) platelets (P<0.05 for both). Administration of NTG/ascorbate attenuated both NO and O2*- release in platelets. CONCLUSIONS: Three days of continuous transdermal administration of NTG was accompanied by increased platelet NO and O2*- production and NADH oxidase activity that was suppressed by coadministration of oral ascorbate. Although a significant degree of tolerance would be expected during continuous nitrate administration, a residual hemodynamic action could be identified by arterial pulse contour analysis.