Home-based family caregiver-delivered music and reading interventions for people living with dementia (HOMESIDE trial): an international randomised controlled trial.

Background: Music interventions provided by qualified therapists within residential aged care are effective at attenuating behavioural and psychological symptoms (BPSD) of people with dementia (PwD). The impact of music interventions on dementia symptom management when provided by family caregivers is unclear. Methods: We implemented a community-based, large, pragmatic, international, superiority, single-masked randomised controlled trial to evaluate if caregiver-delivered music was superior to usual care alone (UC) on reducing BPSD of PwD measured by the Neuropsychiatric Inventory-Questionnaire (NPI-Q). The study included an active control (reading). People with dementia (NPI-Q score ≥6) and their caregiver (dyads) from one of five countries were randomly allocated to caregiver-delivered music, reading, or UC with a 1:1:1 allocation stratified by site. Caregivers received three online protocolised music or reading training sessions delivered by therapists and were recommended to provide five 30-min reading or music activities per week (minimum twice weekly) over 90-days. The NPI-Q severity assessment of PwD was completed online by masked assessors at baseline, 90- (primary) and 180-days post-randomisation and analysed on an intention-to-treat basis using a likelihood-based longitudinal data analysis model. ACTRN12618001799246; ClinicalTrials.govNCT03907748. Findings: Between 27th November 2019 and 7th July 2022, we randomised 432 eligible of 805 screened dyads (music n = 143, reading n = 144, UC n = 145). There was no statistical or clinically important difference in the change from baseline BPSD between caregiver-delivered music (-0.15, 95% CI -1.41 to 1.10, p = 0.81) or reading (-1.12, 95% CI -2.38 to 0.14, p = 0.082) and UC alone at 90-days. No related adverse events occurred. Interpretation: Our findings suggested that music interventions and reading interventions delivered by trained caregivers in community contexts do not decrease enduring BPSD symptoms. Funding: Our funding was provided by National Health and Medical Research Council, Australia; The Research Council of Norway; Federal Ministry of Education and Research, Germany; National Centre for Research and Development, Poland; Alzheimer's Society, UK, as part of the Joint Programme for Neurodegenerative Diseases consortia scheme.

Statistical analysis plan for HOMESIDE: a randomised controlled trial for home-based family caregiver-delivered music and reading interventions for people living with dementia.

BACKGROUND: Most people with dementia live in the community, not in residential care. Therefore, quality informal care for them is critical for managing behavioural and psychological symptoms of dementia (BPSD). Music therapy has been shown to reduce BPSD. However, no randomised controlled trial has examined the effects of music interventions delivered by caregivers in home settings. The HOME-based caregiver-delivered music intervention for people living with dementia (HOMESIDE) trial aims to evaluate the effectiveness of a 12-week music intervention in addition to standard care for BPSD. This article describes the statistical analysis plan. METHODS AND ANALYSIS: HOMESIDE is a large, pragmatic international three-arm parallel-group randomised controlled trial. Dyads (persons with dementia and caregiver) in Australia, Germany, the UK, Poland and Norway were randomised to receive music and standard care, reading and standard care or standard care alone. The primary outcome is BPSD (proxy) of the person living with dementia, measured using the Neuropsychiatric Inventory-Questionnaire (NPI-Q) at 90 and 180 days post-randomisation. Longitudinal analysis will compare NPI-Q severity between music and standard care versus standard care alone. Secondary outcomes include quality of life and depression (both person with dementia and caregiver), cognition (person with dementia only), distress, resilience, competence and caregiver-patient relationship (caregiver only). Treatment effects will be obtained at 90 and 180 days post-randomisation, where applicable. Safety outcomes (adverse events, hospitalisations, deaths) will be summarised. DISCUSSION: This statistical analysis plan provides a detailed methodology for the analysis of HOMESIDE and will improve the validity of the study and reduce the potential for bias. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry ACTRN12618001799246. Registered on November 05, 2018. CLINICALTRIALS: gov NCT03907748. Registered on April 09, 2019.

A protocol for a prospective, multicentre observational study to determine if nonanaemic iron deficiency worsens postoperative outcome in patients undergoing elective surgery for resection of colorectal cancer: The NATO study.

BACKGROUND: Preoperative absolute and functional iron deficiency anaemia is associated with poor postoperative outcomes in patients undergoing surgery for colorectal cancer. It is biologically plausible that "early", or "nonanaemic" iron deficiency may also be associated with worse postoperative outcomes in similar cohorts, albeit at lesser severity than that seen for anaemia. The evidence supporting this assertion is of low quality. METHODS: We have designed a prospective, observational study to delineate associations between preoperative non-anaemic iron deficiency and postoperative outcomes after surgery for colorectal cancer. Patients without anaemia, undergoing elective surgery for colorectal cancer will be allocated to an iron replete or an iron deficient group based on preoperative transferrin saturation. The primary outcome is days alive and at home on postoperative day 90. Secondary outcomes include days alive and at home on postoperative day 30, length of hospital stay, readmission to acute care, postoperative complications, health-related quality of life scores, quality of postoperative recovery, and requirement for allogeneic blood transfusion. The planned sample size is 422 patients, which has 80% power to detect a two-day difference in the primary outcome. The study commenced in May 2019. CONCLUSION: The results of this study will provide patients and clinicians with high-quality evidence concerning associations between nonanaemic iron deficiency and patient-centred outcomes after surgery for colorectal cancer. The study will be conducted in multiple urban and rural centres across Australia and New Zealand. The results will be highly generalisable to contemporary surgical practice and should be rapidly translated.

Associations between non-anaemic iron deficiency and outcomes following elective cardiac surgery (IDOCS): a prospective cohort study.

BACKGROUND: One in two adults undergoing cardiac surgery are iron deficient, best practice guidelines and consensus statements recommend routine investigation and treatment of iron deficiency before elective cardiac surgery, even in the absence of anaemia; however, it is not clear if non-anaemic iron deficiency is associated with worse outcomes in this patient population. We hypothesised that iron deficiency would be associated with worse postoperative outcomes than an iron replete state in adults without anaemia undergoing elective cardiac surgery. METHODS: We performed a prospective, cohort study at two hospitals in Australia. We recruited adults (ie, people 18 years and older) undergoing elective cardiac surgery without anaemia (defined as a haemoglobin of less than 130 g/L for men and less than 120 g/L for women), concomitant haemoglobinopathy, bone marrow pathology, haemochromatosis, or end-stage renal failure requiring dialysis. Participants were stratified as iron deficient or iron replete on the basis of preoperative testing. Iron deficiency was defined as a serum ferritin of less than 100 µg/L or 100-300 µg/L if transferrin saturation was less than 20% or C-reactive protein was more than 5 mg/L. The primary endpoint was days alive and at home at postoperative day 30. The primary analysis included all patients with data available for the primary endpoint and was adjusted for risk measured using EuroSCORE-II and body surface area. The study was prospectively registered with the Australian and New Zealand Clinical Trials Registry, ACTRN12618000185268. FINDINGS: We conducted the study between Feb 21, 2018, and May 7, 2021. We assessed 1171 patients for eligibility and 691 were ineligible; therefore, we enrolled and followed up 480 participants. 240 (50%) were iron deficient and 240 (50%) were iron replete, 95 (20%) were women, 385 (80%) were men, and 453 (94%) were White. Complete data was available for 479 individuals (240 in the iron deficient group and 239 in the iron replete group) for the primary endpoint. The iron deficient group had a median of 22·87 days (IQR 20·65 to 24·06) alive and at home at postoperative day 30, and the iron replete group had a median of 23·18 days (IQR 20·69 to 24·70). The unadjusted difference in medians between the groups was -0·18 days (95% CI -0·73 to 0·36; p=0·51) and the adjusted difference in medians between the groups was -0·11 days (95% CI -0·66 to 0·45; p=0·70). INTERPRETATION: In non-anaemic adults undergoing elective cardiac surgery, our findings suggest that patients with iron deficiency do not have a reduction in days alive and at home at postoperative day 30 compared with patients who have a normal iron status. Routine preoperative investigation for iron deficiency in patients without anaemia undergoing elective cardiac surgery using the definitions we tested might be low-value care. FUNDING: Australian and New Zealand College of Anaesthetists Foundation.