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15. Prophylactic melatonin for delirium in intensive care (Pro-MEDIC): a randomized controlled trial

Author

Wibrow, Bradley, Martinez, F. Eduardo, Myers, Erina, Chapman, Andrew, Litton, Edward, Ho, Kwok. M., and Regli, Adrian

Subjects
Medical research -- Analysis -- Usage -- Health aspects, Medicine, Experimental -- Analysis -- Usage -- Health aspects, Mortality -- Australia, Melatonin -- Research, Clinical trials -- Health aspects -- Research -- Usage -- Analysis, Delirium -- Research, Health care industry
Abstract

Purpose Delirium is common in the critically ill, highly distressing to patients and families and associated with increased morbidity and mortality. Results of studies on preventative use of melatonin in various patient groups have produced mixed results. The aim of this study was to determine whether administration of melatonin decreases the prevalence of delirium in critically ill patients. Methods Multicentre, randomized, placebo-controlled, double-blind trial across 12 Australian ICUs recruiting patients from July 2016 to September 2019. Patients of at least 18 years requiring ICU admission with an expected length of stay (LOS) greater than 72 h; enrolled within 48 h of ICU admission. Indistinguishable liquid melatonin (4 mg; n = 419) or placebo (n = 422) was administered enterally at 21:00 h for 14 consecutive nights or until ICU discharge. The primary outcome was the proportion of delirium-free assessments, as a marker of delirium prevalence, within 14 days or before ICU discharge. Delirium was assessed twice daily using the Confusion Assessment Method for ICU (CAM-ICU) score. Secondary outcomes included sleep quality and quantity, hospital and ICU LOS, and hospital and 90-day mortality. Results A total of 847 patients were randomized into the study with 841 included in data analysis. Baseline characteristics of the participants were similar. There was no significant difference in the average proportion of delirium-free assessments per patient between the melatonin and placebo groups (79.2 vs 80% respectively, p = 0.547). There was no significant difference in any secondary outcomes including ICU LOS (median: 5 vs 5 days, p = 0.135), hospital LOS (median: 14 vs 12 days, p = 0816), mortality at any time point including at 90 days (15.5 vs 15.6% p = 0.948), nor in the quantity or quality of sleep. There were no serious adverse events reported in either group. Conclusion Enteral melatonin initiated within 48 h of ICU admission did not reduce the prevalence of delirium compared to placebo. These findings do not support the routine early use of melatonin in the critically ill., Author(s): Bradley Wibrow [sup.1] [sup.2], F. Eduardo Martinez [sup.3] [sup.4], Erina Myers [sup.1] [sup.5], Andrew Chapman [sup.6], Edward Litton [sup.2] [sup.7], Kwok. M. Ho [sup.2] [sup.6] [sup.19], Adrian Regli [sup.2] [...]

Published
2022
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27. A simplified (modified) Duke Activity Status Index (M-DASI) to characterise functional capacity: a secondary analysis of the Measurement of Exercise Tolerance before Surgery (METS) study

Author

Wallace, S., Thompson, B., Ellis, M., Borg, B., Kerridge, R.K., Douglas, J., Brannan, J., Pretto, J., Godsall, M.G., Beauchamp, N., Allen, S., Kennedy, A., Wright, E., Malherbe, J., Ismail, H., Riedel, B., Melville, A., Sivakumar, H., Murmane, A., Kenchington, K., Kirabiyik, Y., Gurunathan, U., Stonell, C., Brunello, K., Steele, K., Tronstad, O., Masel, P., Dent, A., Smith, E., Bodger, A., Abolfathi, M., Sivalingam, P., Hall, A., Painter, T.W., Macklin, S., Elliott, A., Carrera, A.M., Terblanche, N.C.S., Pitt, S., Samuels, J., Wilde, C., Leslie, K., MacCormick, A., Bramley, D., Southcott, A.M., Grant, J., Taylor, H., Bates, S., Towns, M., Tippett, A., Marshall, F., Mazer, C.D., Kunasingam, J., Yagnik, A., Crescini, C., Yagnik, S., McCartney, C.J.L., Choi, S., Somascanthan, P., Flores, K., Au, S., Beattie, W.S., Karkouti, K., Clarke, H.A., Jerath, A., McCluskey, S.A., Wasowicz, M., Day, L., Pazmino-Canizares, J., Oh, P., Belliard, R., Lee, L., Dobson, K., Chan, V., Brull, R., Ami, N., Stanbrook, M., Hagen, K., Campbell, D., Short, T., Van Der Westhuizen, J., Higgie, J.K., Lindsay, H., Jang, R., Wong, C., Mcallister, D., Ali, M., Kumar, J., Waymouth, E., Kim, C., Dimech, J., Lorimer, M., Tai, J., Miller, R., Sara, R., Collingwood, A., Olliff, S., Gabriel, S., Houston, H., Dalley, P., Hurford, S., Hunt, A., Andrews, L., Navarra, L., Jason-Smith, A., Thompson, H., McMillan, N., Back, G., Lum, M., Martin, D., S James, S., Filipe, H., Pinto, M., Kynaston, S., Phull, M., Beilstein, C., Bodger, P., Everingham, K., Hu, Y., Niebrzegowska, E., Corriea, C., Creary, T., Januszewska, M., Ahmad, T., Whalley, J., Haslop, R., McNeil, J., Brown, A., MacDonald, N., Pakats, M., Greaves, K., Jhanji, S., Raobaikady, R., Black, E., Rooms, M., Lawrence, H., Koutra, M., Pirie, K., Gertsman, M., Jack, S., Celinski, M., Levett, D., Edwards, M., Salmon, K., Bolger, C., Loughney, L., Seaward, L., Collins, H., Tyrell, B., Tantony, N., Golder, K., Ackland, G.L., Stephens, R.C.M., Gallego-Paredes, L., Reyes, A., Gutierrez del Arroyo, A., Raj, A., R Lifford, R., Melo, M., Mamdani, M., Hillis, G., Wijeysundera, H.C., Riedel, Bernhard, Li, Michael H-G., Lee, C.H. Angus, Ismail, Hilmy, Cuthbertson, Brian H., Wijeysundera, Duminda N., and Ho, Kwok M.

Published
2021
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37. Monitoring anti-Xa Levels to Optimize Low-Molecular-Weight-Heparin Thromboprophylaxis in High-Risk Hospitalized Patients: A Stratified Meta-Analysis.

Author

John, Sunil, Wilkinson, Molly, and Ho, Kwok M.

Subjects
THROMBOEMBOLISM prevention, ENOXAPARIN, VEINS, META-analysis, CONFIDENCE intervals, ANTICOAGULANTS, PATIENT monitoring, RISK assessment, TREATMENT effectiveness, FIBRIN, LOW-molecular-weight heparin, THROMBOEMBOLISM, HOSPITAL care, DOSE-effect relationship in pharmacology, DESCRIPTIVE statistics, RESEARCH funding, ODDS ratio, EVALUATION
Abstract

It is uncertain whether monitoring or targeting anti-Xa levels is necessary when using low-molecular-weight-heparin (LMWH) to prevent venous thromboembolism (VTE). This stratified meta-analysis assessed whether monitoring trough or peak anti-Xa levels with LMWH dosing would reduce risk of VTE. Twelve non-randomized studies involving 3604 hospitalized patients met the inclusion criteria and were subject to meta-analysis. Eight studies assessed the association between VTE and peak anti-Xa levels (between.2 and.5 IU/ml) and four studies assessed the benefits of targeting the trough anti-Xa levels (>.1 IU/ml). Achieving an adequate peak or trough anti-Xa level was associated with a reduced risk of VTE (random-effects model odds ratio [OR].52, 95% confidence interval [CI].34-.77; P =.001, I2 = 30% and P -value for heterogeneity =.171) compared with using a fixed standard dose of LMWH. Targeting the trough level (OR.40, 95%CI 0.22–.75, P =.004) appeared to be more effective than targeting the peak level (OR.62, 95%CI 0.37–1.03, P =.066), although a formal interaction analysis did not confirm they were statistically different (ratio of ORs = 1.52, 95%CI 0.68–3.40; z score = 1.03, P =.306). Targeting a higher anti-Xa level did not appear to increase the risk of bleeding or transfusion (OR 1.20, 95%CI 0.46–3.17, P =.707). [ABSTRACT FROM AUTHOR]

Published
2024
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46. Rebleeding following aneurysmal subarachnoid hemorrhage before ‘endovascular first’ treatment: a retrospective case-control study of published scoring systems

Author

Dissanayake, Arosha S, Burrows, Emalee, Ho, Kwok M, Phillips, Timothy J, Honeybul, Stephen, and Hankey, Graeme J

Abstract

BackgroundPre-treatment re-bleeding following aneurysmal subarachnoid hemorrhage (aSAH) affects up to 7.2% of patients even with ultra-early treatment within 24 hours. We retrospectively compared the utility of three published re-bleed prediction models and individual predictors between cases who re-bled matched to controls using size and parent vessel location from a cohort of patients treated in an ultra-early, ‘endovascular first’ manner.MethodsOn retrospective analysis of our 9-year cohort of 707 patients suffering 710 episodes of aSAH, there were 53 episodes of pre-treatment re-bleeding (7.5%). Forty-seven cases who had a single culprit aneurysm were matched to 141 controls. Demographic, clinical and radiological data were extracted and predictive scores calculated. Univariate, multivariate, area under the receiver operator characteristic curve (AUROCC) and Kaplan–Meier (KM) survival curve analyses were performed.ResultsThe majority of patients (84%) were treated using endovascular techniques at a median 14.5 hours post-diagnosis. On AUROCC analysis the score of Liu et al.had minimal utility (C-statistic 0.553, 95% confidence interval (CI) 0.463 to 0.643) while the risk score of Oppong et al.(C-statistic 0.645 95% CI 0.558 to 0.732) and the ARISE-extended score of van Lieshout et al.(C-statistic 0.53 95% CI 0.562 to 0.744) had moderate utility. On multivariate modeling, the World Federation of Neurosurgical Societies (WFNS) grade was the most parsimonious predictor of re-bleeding (C-statistic 0.740, 95% CI 0.664 to 0.816).ConclusionsFor aSAH patients treated in an ultra-early timeframe matched on size and parent vessel location, WFNS grade was superior to three published models for re-bleed prediction. Future re-bleed prediction models should incorporate the WFNS grade.

Published
2024
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50. Flattening the biological age curve by improving metabolic health: to taurine or not to taurine, that’s the question.

Author

Ho, Kwok M., Anna Lee, William Wu, Chan, Matthew T. V., Lowell Ling, Lipman, Jeffrey, Roberts, Jason, Litton, Edward, Joynt, Gavin M., and Martin Wong

Subjects
BIOMARKERS, ENERGY metabolism, COGNITION disorders, FRAIL elderly, MYOCARDIAL ischemia, DIABETES, BLOOD sugar, DNA methylation, CELLULAR aging, AGING, QUALITY assurance, ALKANES, QUALITY of life, AMINO acids
Abstract

The aging population is an important issue around the world especially in developed countries. Although medical advances have substantially extended life span, the same cannot be said for the duration of health span. We are seeing increasing numbers of elderly people who are frail and/or have multiple chronic conditions; all of these can affect the quality of life of the elderly population as well as increase the burden on the healthcare system. Aging is mechanistically related to common medical conditions such as diabetes mellitus, ischemic heart disease, cognitive decline, and frailty. A recently accepted concept termed ‘Accelerated Biological Aging’ can be diagnosed when a person’s biological age—as measured by biomarkers of DNA methylation —is older than their corresponding chronological age. Taurine, a conditionally essential amino acid, has received much attention in the past few years. A substantial number of animal studies have provided a strong scientific foundation suggesting that this amino acid can improve cellular and metabolic health, including blood glucose control, so much that it has been labelled one of the ‘longevity amino acids’. In this review article, we propose the rationale that an adequately powered randomized-controlled-trial (RCT) is needed to confirm whether taurine can meaningfully improve metabolic and microbiome health, and biological age. This trial should incorporate certain elements in order to provide the much-needed evidence to guide doctors, and also the community at large, to determine whether this promising and inexpensive amino acid is useful in improving human metabolic health. [ABSTRACT FROM AUTHOR]

Published
2023
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