The immune cell transcriptome is modulated by vitamin D3 supplementation in people with a first demyelinating event participating in a randomized placebo-controlled trial.

Vitamin D deficiency is a risk factor for developing multiple sclerosis. The PrevANZ trial was conducted to determine if vitamin D3 supplementation can prevent recurrent disease activity in people with a first demyelinating event. As a sub-study of this trial, we investigated the effect of supplementation on peripheral immune cell gene expression. Participants were randomized to 1000, 5000 or 10,000 international units daily of vitamin D3 or placebo. Peripheral blood was collected at baseline and 12 weeks and sent for ribonucleic acid sequencing. Datasets from 55 participants were included. Gene expression was modulated by high dose supplementation. Antigen presentation and viral response pathways were upregulated. Oxidative phosphorylation and immune signaling pathways, including tumor necrosis factor-alpha and interleukin-17 signaling, were downregulated. Overall, vitamin D3 supplementation for 12 weeks modulated the peripheral immune cell transcriptome with induction of anti-inflammatory gene expression profiles. Our results support a dose-dependent effect of vitamin D3 supplementation on immune gene expression.

Vitamin D did not reduce multiple sclerosis disease activity after a clinically isolated syndrome.

Low serum levels of 25-hydroxyvitamin D (25(OH)D), and low sunlight exposure, are known risk factors for the development of multiple sclerosis. Add-on vitamin D supplementation trials in established multiple sclerosis have been inconclusive. The effects of vitamin D supplementation to prevent multiple sclerosis is unknown. We aimed to test the hypothesis that oral vitamin D3 supplementation in high-risk clinically isolated syndrome (abnormal MRI, at least three T2 brain and/or spinal cord lesions), delays time to conversion to definite multiple sclerosis, that the therapeutic effect is dose-dependent, and that all doses are safe and well tolerated. We conducted a double-blind trial in Australia and New Zealand. Eligible participants were randomised 1:1:1:1 to placebo, 1000, 5000, or 10 000 IU of oral vitamin D3 daily within each study centre (n=23) and followed for up to 48 weeks. Between 2013 and 2021, we enrolled 204 participants. Brain MRI scans were performed at baseline, 24 and 48 weeks. The main study outcome was conversion to clinically definite multiple sclerosis based on the 2010 McDonald criteria defined as either a clinical relapse or new brain MRI T2 lesion development. We included 199 cases in the intention-to-treat analysis based on assigned dose. Of these, 116 converted to multiple sclerosis by 48 weeks (58%). Compared to placebo, the HRs (95%CI) for conversion were 1000 IU 0.87 (0.50, 1.50); 5000 IU 1.37 (0.82, 2.29); and 10 000 IU 1.28 (0.76, 2.14). In an adjusted model including age, sex, latitude, study centre, and baseline symptom number, clinically isolated syndrome onset site, presence of infratentorial lesions, and use of steroids, the HRs (versus placebo) were 1000 IU 0.80 (0.45, 1.44); 5000 IU 1.36 (0.78, 2.38); 10 000 IU 1.07 (0.62, 1.85). Vitamin D3 supplementation was safe and well tolerated. We did not demonstrate reduction in multiple sclerosis disease activity by vitamin D3 supplementation after a high-risk clinically isolated syndrome. Trial registration Australian Clinical Trials Registration Number ACTRN12612001160820.

Clinical staff perceptions on the quality of end-of-life care in an Australian acute private hospital: a cross-sectional survey.

Objective To explore the perceptions of clinical staff on the quality of end-of-life care in an acute private hospital. Methods A descriptive cross-sectional study with a convenience sample of clinical staff in an acute private hospital were surveyed using a validated end-of-life survey. Data from the surveys were analysed using descriptive statistics for quantitative responses and inductive content analysis for the open-ended responses. Results Overall, 133 staff completed the survey. Of these, 107 had cared for a dying patient in the hospital. In total, 87.6% of participants felt confident in their ability to recognise a dying patient and 66.7% felt confident in their ability to talk to the patient and family. Almost one-third had not received specific training in the area. Conclusions Hospitals need to take the lead in ensuring end-of-life care processes are embedded across clinical areas. This includes providing staff with end-of-life care education and support in the delivery of end-of-life care. These strategies will facilitate safe and quality end-of-life care, including better collaboration between patients, families and staff. What is known about the topic? Key to providing quality end-of-life care in hospitals are strategic guidelines that support good clinical governance and adequately trained staff to deliver the care. What does the paper add? This study highlights the importance of clinical staff in all areas having skills and confidence in providing care to dying patients and their families. What are the implications for practitioners? It is important that all health practitioners implement strategies to overcome gaps in staff education and support, to ensure all patients and families receive quality end-of-life care.

Improving the safety and quality of end-of-life in an Australian private hospital setting: An audit of documented end-of-life care.

OBJECTIVE: This study reviewed the audit outcomes of the documented end-of-life care in a private hospital against the Australian Commission on Safety and Quality in Health Care's five recommended processes of care (Essential Elements (EE) 1-5). METHODS: A retrospective database review of deaths over a three-year period was undertaken. This was followed by a sequential medical record audit (n = 100) to evaluate the end-of-life care documented in the three days preceding death. RESULTS: There were 997 deaths from 2015 to 2017. The audit found communication to family the patient was dying (91%) and to the patient (36%) (EE1); evidence of specialist referral (68%) (EE2); assessment of the ability to eat/drink in the last 72 hours (86%) (EE3); advance care directives (13%) and hospital resuscitation plans (92%) (EE4); and response to patient or family concerns (100%) (EE5). CONCLUSIONS: Components of the processes of care of the Essential Elements need to be addressed to improve patient-centred communication and shared decision-making.