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1.
The effects of probiotics administration during pregnancy on preeclampsia and associated maternal, fetal, and newborn outcomes: a systematic review and meta-analysis.
McDougall, A, Nguyen, R, Nguyen, PY, Allen, C, Cheang, S, Makama, M, Mills, K, Hastie, R, Ammerdorffer, A, Gulmezoglu, AM, et al
American journal of obstetrics & gynecology MFM. 2024;(4):101322
Abstract
OBJECTIVE This study aimed to synthesize the available evidence on probiotic administration during pregnancy for the prevention of preeclampsia and its effects on related maternal, fetal, and newborn outcomes. DATA SOURCES Six databases were systematically searched for eligible studies, namely Ovid MEDLINE, Embase, CINAHL, Cochrane, Global Index Medicus, and the Maternity and Infant Care Database, from inception to August 2, 2023. STUDY ELIGIBILITY CRITERIA Randomized controlled trials that evaluated the effects of probiotic administration on women during any stage of pregnancy were eligible for inclusion. METHODS The protocol was registered with the International Prospective Register of Systematic Reviews under identifier CRD42023421613. Evaluating study eligibility, extracting data, assessing risk of bias (ROB-2 tool), and rating certainty (Grading of Recommendations, Assessment, Development and Evaluations) were conducted independently by 2 authors. The primary outcomes were incidence of preeclampsia, eclampsia, and maternal mortality. A meta-analysis was performed, and the results were reported as risk ratios with 95% confidence intervals. RESULTS A total of 29 trials (7735 pregnant women) met the eligibility criteria. There was heterogeneity across the trials in the population of enrolled women and the type of probiotic tested (20 different strains), although most used oral administration. Probiotics may make no difference to the risk of preeclampsia (risk ratio, 1.14; 95% confidence interval, 0.84-1.53; 11 trials; 2401 women; low certainty evidence), preterm birth at <37 weeks' gestation (risk ratio, 0.93; 95% confidence interval, 0.66-1.30; 18 trials, 4016 women; low certainty evidence), or gestational age at delivery (mean difference, -0.03 weeks [≈0.2 days]; 95% confidence interval, -0.16 to 0.10 weeks [≈ -1.1 to 0.7 days]; 13 trials, 2194 women; low certainty evidence). It is difficult to assess the effects of probiotics on other secondary outcomes because the evidence was of very low certainty, however, no benefits or harms were observed. CONCLUSION Limited evidence suggests that probiotic supplementation does not affect the risk for preeclampsia. Further high-quality trials are needed to definitively assess the benefits and possible harms of probiotic supplementation during pregnancy. There is also a lack of data from trials that included women who were undernourished or who experienced microbial dysbiosis and for whom probiotic supplementation might be useful.
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2.
The Health4Life e-health intervention for modifying lifestyle risk behaviours of adolescents: secondary outcomes of a cluster randomised controlled trial.
O'Dean, S, Sunderland, M, Newton, N, Gardner, L, Teesson, M, Chapman, C, Thornton, L, Slade, T, Hides, L, McBride, N, et al
The Medical journal of Australia. 2024
Abstract
OBJECTIVES To investigate the effectiveness of a school-based multiple health behaviour change e-health intervention for modifying risk factors for chronic disease (secondary outcomes). STUDY DESIGN Cluster randomised controlled trial. SETTING, PARTICIPANTS Students (at baseline [2019]: year 7, 11-14 years old) at 71 Australian public, independent, and Catholic schools. INTERVENTION Health4Life: an e-health school-based multiple health behaviour change intervention for reducing increases in the six major behavioural risk factors for chronic disease: physical inactivity, poor diet, excessive recreational screen time, poor sleep, and use of alcohol and tobacco. It comprises six online video modules during health education class and a smartphone app. MAIN OUTCOME MEASURES Comparison of Health4Life and usual health education with respect to their impact on changes in twelve secondary outcomes related to the six behavioural risk factors, assessed in surveys at baseline, immediately after the intervention, and 12 and 24 months after the intervention: binge drinking, discretionary food consumption risk, inadequate fruit and vegetable intake, difficulty falling asleep, and light physical activity frequency (categorical); tobacco smoking frequency, alcohol drinking frequency, alcohol-related harm, daytime sleepiness, and time spent watching television and using electronic devices (continuous). RESULTS A total of 6640 year 7 students completed the baseline survey (Health4Life: 3610; control: 3030); 6454 (97.2%) completed at least one follow-up survey, 5698 (85.8%) two or more follow-up surveys. Health4Life was not statistically more effective than usual school health education for influencing changes in any of the twelve outcomes over 24 months; for example: fruit intake inadequate: odds ratio [OR], 1.08 (95% confidence interval [CI], 0.57-2.05); vegetable intake inadequate: OR, 0.97 (95% CI, 0.64-1.47); increased light physical activity: OR, 1.00 (95% CI, 0.72-1.38); tobacco use frequency: relative difference, 0.03 (95% CI, -0.58 to 0.64) days per 30 days; alcohol use frequency: relative difference, -0.34 (95% CI, -1.16 to 0.49) days per 30 days; device use time: relative difference, -0.07 (95% CI, -0.29 to 0.16) hours per day. CONCLUSIONS Health4Life was not more effective than usual school year 7 health education for modifying adolescent risk factors for chronic disease. Future e-health multiple health behaviour change intervention research should examine the timing and length of the intervention, as well as increasing the number of engagement strategies (eg, goal setting) during the intervention. TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry: ACTRN12619000431123 (prospective).
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3.
The Differential Translation Capabilities of the Human DHFR2 Gene Indicates a Developmental and Tissue-Specific Endogenous Protein of Low Abundance.
Bookey, N, Drago, P, Leung, KY, Hughes, L, MacCooey, A, Ozaki, M, Henry, M, De Castro, SCP, Doykov, I, Heywood, WE, et al
Molecular & cellular proteomics : MCP. 2024;(3):100718
Abstract
A functional role has been ascribed to the human dihydrofolate reductase 2 (DHFR2) gene based on the enzymatic activity of recombinant versions of the predicted translated protein. However, the in vivo function is still unclear. The high amino acid sequence identity (92%) between DHFR2 and its parental homolog, DHFR, makes analysis of the endogenous protein challenging. This paper describes a targeted mass spectrometry proteomics approach in several human cell lines and tissue types to identify DHFR2-specific peptides as evidence of its translation. We show definitive evidence that the DHFR2 activity in the mitochondria is in fact mediated by DHFR, and not DHFR2. Analysis of Ribo-seq data and an experimental assessment of ribosome association using a sucrose cushion showed that the two main Ensembl annotated mRNA isoforms of DHFR2, 201 and 202, are differentially associated with the ribosome. This indicates a functional role at both the RNA and protein level. However, we were unable to detect DHFR2 protein at a detectable level in most cell types examined despite various RNA isoforms of DHFR2 being relatively abundant. We did detect a DHFR2-specific peptide in embryonic heart, indicating that the protein may have a specific role during embryogenesis. We propose that the main functionality of the DHFR2 gene in adult cells is likely to arise at the RNA level.
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4.
Health4Life eHealth intervention to modify multiple lifestyle risk behaviours among adolescent students in Australia: a cluster-randomised controlled trial.
Champion, KE, Newton, NC, Gardner, LA, Chapman, C, Thornton, L, Slade, T, Sunderland, M, Hides, L, McBride, N, O'Dean, S, et al
The Lancet. Digital health. 2023;(5):e276-e287
Abstract
BACKGROUND Lifestyle risk behaviours are prevalent among adolescents and commonly co-occur, but current intervention approaches tend to focus on single risk behaviours. This study aimed to evaluate the efficacy of the eHealth intervention Health4Life in modifying six key lifestyle risk behaviours (ie, alcohol use, tobacco smoking, recreational screen time, physical inactivity, poor diet, and poor sleep, known as the Big 6) among adolescents. METHODS We conducted a cluster-randomised controlled trial in secondary schools that had a minimum of 30 year 7 students, in three Australian states. A biostatistician randomly allocated schools (1:1) to Health4Life (a six-module, web-based programme and accompanying smartphone app) or an active control group (usual health education) with the Blockrand function in R, stratified by site and school gender composition. All students aged 11-13 years who were fluent in English and attended participating schools were eligible. Teachers, students, and researchers were not masked to allocation. Primary outcomes were alcohol use, tobacco use, recreational screen time, moderate to vigorous physical activity (MVPA), sugar-sweetened beverage intake, and sleep duration at 24 months, measured by self-report surveys, and analysed in all students who were eligible at baseline. Latent growth models estimated between-group change over time. This trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12619000431123). FINDINGS Between April 1, 2019, and Sept 27, 2019, we recruited 85 schools (9280 students), of which 71 schools with 6640 eligible students (36 schools [3610 students] assigned to the intervention and 35 [3030 students] to the control) completed the baseline survey. 14 schools were excluded from the final analysis or withdrew, mostly due to a lack of time. We found no between-group differences for alcohol use (odds ratio 1·24, 95% CI 0·58-2·64), smoking (1·68, 0·76-3·72), screen time (0·79, 0·59-1·06), MVPA (0·82, 0·62-1·09), sugar-sweetened beverage intake (1·02, 0·82-1·26), or sleep (0·91, 0·72-1·14) at 24 months. No adverse events were reported during this trial. INTERPRETATION Health4Life was not effective in modifying risk behaviours. Our results provide new knowledge about eHealth multiple health behaviour change interventions. However, further research is needed to improve efficacy. FUNDING Paul Ramsay Foundation, the Australian National Health and Medical Research Council, the Australian Government Department of Health and Aged Care, and the US National Institutes of Health.
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5.
Associations of metabolomic profiles with circulating vitamin E and urinary vitamin E metabolites in middle-aged individuals.
Luo, J, Hashimoto, Y, Martens, LG, Meulmeester, FL, Ashrafi, N, Mook-Kanamori, DO, Rosendaal, FR, Jukema, JW, van Dijk, KW, Mills, K, et al
Nutrition (Burbank, Los Angeles County, Calif.). 2022;:111440
Abstract
Vitamin E (α-tocopherol [α-TOH]) is transported in lipoprotein particles in blood, but little is known about the transportation of its oxidized metabolites. In the Netherlands Epidemiology of Obesity Study, we aimed to investigate the associations of 147 circulating metabolomic measures obtained through targeted nuclear magnetic resonance with serum α-TOH and its urinary enzymatic (α-CEHC) and oxidized (α-TLHQ) metabolites from 24-h urine quantified by liquid chromatography with tandem mass spectrometry. Multivariable linear regression analyses, in which multiple testing was taken into account, were performed to assess associations between metabolomic measures (determinants; standardized to mean = 0, SD = 1) and vitamin E metabolites (outcomes), adjusted for demographic factors. We analyzed 474 individuals (55% women, 45% men) with a mean (SD) age of 55.7 (6.0) y. Out of 147 metabolomic measures, 106 were associated (P < 1.34 × 10-3) with serum α-TOH (median β [interquartile range] = 0.416 [0.383-0.466]), predominantly lipoproteins associated with higher α-TOH. The associations of metabolomic measures with urinary α-CEHC have directions similar to those with α-TOH, but effect sizes were smaller and non-significant (median β [interquartile range] = 0.065 [0.047-0.084]). However, associations of metabolomic measures with urinary α-TLHQ were markedly different from those with both serum α-TOH and urinary α-CEHC, with negative and small-to-null relations to most very-low-density lipoproteins and amino acids. Therefore, our results highlight the differences in the lipoproteins involved in the transportation of circulating α-TOH and oxidized vitamin E metabolites. This indicates that circulating α-TOH may be representative of the enzymatic but not the antioxidative function of vitamin E.
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6.
Association of measures of body fat with serum alpha-tocopherol and its metabolites in middle-aged individuals.
Meulmeester, FL, Luo, J, Martens, LG, Ashrafi, N, de Mutsert, R, Mook-Kanamori, DO, Lamb, HJ, Rosendaal, FR, Willems van Dijk, K, Mills, K, et al
Nutrition, metabolism, and cardiovascular diseases : NMCD. 2021;(8):2407-2415
Abstract
BACKGROUND AND AIMS The accumulation of fat increases the formation of lipid peroxides, which are partly scavenged by alpha-tocopherol (α-TOH). Here, we aimed to investigate the associations between different measures of (abdominal) fat and levels of urinary α-TOH metabolites in middle-aged individuals. METHODS AND RESULTS In this cross-sectional analysis in the Netherlands Epidemiology of Obesity study (N = 511, 53% women; mean [SD] age of 55 [6.1] years), serum α-TOH and α-TOH metabolites from 24-h urine were measured as alpha-tocopheronolactone hydroquinone (α-TLHQ, oxidized) and alpha-carboxymethyl-hydroxychroman (α-CEHC, enzymatically converted) using liquid-chromatography-tandem mass spectrometry. Body mass index and total body fat were measured, and abdominal subcutaneous and visceral adipose tissue (aSAT and VAT) were assessed using magnetic resonance imaging. Using multivariable-adjusted linear regression analyses, we analysed the associations of BMI, TBF, aSAT and VAT with levels of urinary α-TOH metabolites, adjusted for confounders. We observed no evidence for associations between body fat measures and serum α-TOH. Higher BMI and TBF were associated with lower urinary levels of TLHQ (0.95 [95%CI: 0.90, 1.00] and 0.94 [0.88, 1.01] times per SD, respectively) and with lower TLHQ relative to CEHC (0.93 [0.90, 0.98] and 0.93 [0.87, 0.98] times per SD, respectively). We observed similar associations for VAT (TLHQ: 0.94 [0.89, 0.99] times per SD), but not for aSAT. CONCLUSIONS Opposite to our research hypothesis, higher abdominal adiposity was moderately associated with lower levels of oxidized α-TOH metabolites, which might reflect lower vitamin E antioxidative activity in individuals with higher abdominal fat instead.
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7.
Best-practice clinical management of flares in people with osteoarthritis: A scoping review of behavioral, lifestyle and adjunctive treatments.
Bowden, JL, Kobayashi, S, Hunter, DJ, Mills, K, Peat, G, Guillemin, F, Parry, E, Thomas, MJ, Eyles, JP
Seminars in arthritis and rheumatism. 2021;(4):749-760
Abstract
INTRODUCTION Transient episodes of increased pain, stiffness or swelling are common in people with osteoarthritis (OA). Yet, evidence-based management strategies for lessening the impact of OA flares are rarely covered in clinical guidelines and have been identified as a gap by clinicians delivering OA care. We aimed to identify evidence on behavioral, lifestyle or other adjunctive flare management strategies that could be used by clinicians or consumers. MATERIALS AND METHODS A literature search between 1990-2020 was performed in three databases using a scoping methodology. We included qualitative or quantitative studies, and reviews that examined OA flare management, or that reported OA flare outcomes at timepoints ≤2 weeks post-intervention. Outcomes included any physical or psychological OA outcome treatable with a therapeutic intervention. RESULTS We included 9 studies, all of which examined the relationship between therapeutic exercise/ physical activity and OA flares. All studies reported pain outcomes at the knee. Two also included the hip. Only two studies examined specific management strategies for OA flares. Both favorably reported the benefits of undertaking an exercise program modified accordingly during an episode, but the quality of the evidence was low. DISCUSSION This scoping review highlights the paucity of evidence available on non-pharmacological treatments of OA flare management that could influence clinical practice. At present, there is no robust evidence to support or reject any specific therapies for OA flare management in clinical practice. Future work is needed, particularly around outcomes beyond pain, trajectories of symptom improvement, and for joints other than the knee.
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8.
A randomised controlled trial of the effect of providing online risk information and lifestyle advice for the most common preventable cancers.
Masson, G, Mills, K, Griffin, SJ, Sharp, SJ, Klein, WMP, Sutton, S, Usher-Smith, JA
Preventive medicine. 2020;:106154
Abstract
Few trial data are available concerning the impact of personalised cancer risk information on behaviour. This study assessed the short-term effects of providing personalised cancer risk information on cancer risk beliefs and self-reported behaviour. We randomised 1018 participants, recruited through the online platform Prolific, to either a control group receiving cancer-specific lifestyle advice or one of three intervention groups receiving their computed 10-year risk of developing one of the five most common preventable cancers either as a bar chart, a pictograph or a qualitative scale alongside the same lifestyle advice. The primary outcome was change from baseline in computed risk relative to an individual with a recommended lifestyle (RRI)1 at three months. Secondary outcomes included: health-related behaviours, risk perception, anxiety, worry, intention to change behaviour, and a newly defined concept, risk conviction. After three months there were no between-group differences in change in RRI (p = 0.71). At immediate follow-up, accuracy of absolute risk perception (p < 0.001), absolute and comparative risk conviction (p < 0.001) and intention to increase fruit and vegetables (p = 0.026) and decrease processed meat (p = 0.033) were higher in all intervention groups relative to the control group. The increases in accuracy and conviction were only seen in individuals with high numeracy and low baseline conviction, respectively. These findings suggest that personalised cancer risk information alongside lifestyle advice can increase short-term risk accuracy and conviction without increasing worry or anxiety but has little impact on health-related behaviour. Trial registration: ISRCTN17450583. Registered 30 January 2018.
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9.
Study protocol of the Health4Life initiative: a cluster randomised controlled trial of an eHealth school-based program targeting multiple lifestyle risk behaviours among young Australians.
Teesson, M, Champion, KE, Newton, NC, Kay-Lambkin, F, Chapman, C, Thornton, L, Slade, T, Sunderland, M, Mills, K, Gardner, LA, et al
BMJ open. 2020;(7):e035662
Abstract
INTRODUCTION Lifestyle risk behaviours, including alcohol use, smoking, poor diet, physical inactivity, poor sleep (duration and/or quality) and sedentary recreational screen time ('the Big 6'), are strong determinants of chronic disease. These behaviours often emerge during adolescence and co-occur. School-based interventions have the potential to address risk factors prior to the onset of disease, yet few eHealth school-based interventions target multiple behaviours concurrently. This paper describes the protocol of the Health4Life Initiative, an eHealth school-based intervention that concurrently addresses the Big 6 risk behaviours among secondary school students. METHODS AND ANALYSIS A multisite cluster randomised controlled trial will be conducted among year 7 students (11-13 years old) from 72 Australian schools. Stratified block randomisation will be used to assign schools to either the Health4Life intervention or an active control (health education as usual). Health4Life consists of (1) six web-based cartoon modules and accompanying activities delivered during health education (once per week for 6 weeks), and a smartphone application (universal prevention), and (2) additional app content, for students engaging in two or more risk behaviours when they are in years 8 and 9 (selective prevention). Students will complete online self-report questionnaires at baseline, post intervention, and 12, 24 and 36 months after baseline. Primary outcomes are consumption of sugar-sweetened beverages, moderate-to-vigorous physical activity, sleep duration, sedentary recreational screen time and uptake of alcohol and tobacco use. ETHICS AND DISSEMINATION This study has been approved by the University of Sydney (2018/882), NSW Department of Education (SERAP no. 2019006), University of Queensland (2019000037), Curtin University (HRE2019-0083) and relevant Catholic school committees. Results will be presented to schools and findings disseminated via peer-reviewed journals and scientific conferences. This will be the first evaluation of an eHealth intervention, spanning both universal and selective prevention, to simultaneously target six key lifestyle risk factors among adolescents. TRIAL REGISTRATION NUMBER Australian New Zealand Clinical Trials Registry (ACTRN12619000431123), 18 March 2019.
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10.
Comparative effects of lipid lowering, hypoglycemic, antihypertensive and antiplatelet medications on carotid artery intima-media thickness progression: a network meta-analysis.
Huang, R, Mills, K, Romero, J, Li, Y, Hu, Z, Cao, Y, Huang, H, Xu, Y, Jiang, L
Cardiovascular diabetology. 2019;(1):14
Abstract
BACKGROUND Carotid artery intima-media thickness (cIMT) progression is a surrogate marker of atherosclerosis with a high predictive value for future CVD risk. This study evaluates the comparative efficacies of lipid lowering, hypoglycemic, antihypertensive and antiplatelet medications on cIMT progression. METHODS We conducted a network meta-analysis (NMA) to evaluate the relative efficacies of several drug classes in modifying cIMT progression. After a literature search in several electronic databases, studies were selected by following predetermined eligibility criteria. An inverse variance-heterogeneity model was used for NMA. Sensitivity analyses were performed to check the reliability of the overall NMA, and transitivity analyses were performed to examine the effects of modifiers on the NMA outcomes. RESULTS Data were taken from 47 studies (15,721 patients; age: 60.2 years [95% confidence interval (CI) 58.8, 61.6]; BMI: 27.2 kg/m2 [95% CI 26.4, 28.0]; and gender: 58.3% males [95% CI 48.3, 68.3]). Treatment duration was 25.8 months [95% CI 22.9, 28.7]. Of the 13 drug classes in the network, treatment with phosphodiesterase III inhibitors was the most effective in retarding annual mean cIMT against network placebo (weighted mean difference (WMD) - 0.059 mm [95% CI - 0.099, - 0.020) followed by the calcium channel blockers (WMD - 0.055 mm [95% CI - 0.099, 0.001]) and platelet adenosine diphosphate inhibitors (WMD - 0.033 mm [95% CI - 0.058, 0.008]). These 3 drug classes also attained the same positions when the NMA was conducted by using first-year changes in mean cIMT. In transitivity analyses, longer treatment duration, higher body mass index (BMI), and a higher baseline cIMT were found to be independently associated with a lesser reduction in annual mean cIMT. However, in a multivariate analysis with these 3 modifiers, none of these factors was significantly associated with annual change in mean cIMT. In the placebo group, age was inversely associated with annual change in mean cIMT independently. CONCLUSION Phosphodiesterase III inhibitors and calcium channel blockers are found more effective than other drug classes in retarding cIMT progression. Age, BMI, and baseline cIMT may have some impact on these outcomes.