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Anticholinergic deprescribing interventions for reducing risk of cognitive decline or dementia in older adults with and without prior cognitive impairment.
Taylor-Rowan, M, Alharthi, AA, Noel-Storr, AH, Myint, PK, Stewart, C, McCleery, J, Quinn, TJ
The Cochrane database of systematic reviews. 2023;(12):CD015405
Abstract
BACKGROUND Anticholinergics are medications that block the action of acetylcholine in the central or peripheral nervous system. Medications with anticholinergic properties are commonly prescribed to older adults. The cumulative anticholinergic effect of all the medications a person takes is referred to as the anticholinergic burden. A high anticholinergic burden may cause cognitive impairment in people who are otherwise cognitively healthy, or cause further cognitive decline in people with pre-existing cognitive problems. Reducing anticholinergic burden through deprescribing interventions may help to prevent onset of cognitive impairment or slow the rate of cognitive decline. OBJECTIVES Primary objective • To assess the efficacy and safety of anticholinergic medication reduction interventions for improving cognitive outcomes in cognitively healthy older adults and older adults with pre-existing cognitive issues. Secondary Objectives • To compare the effectiveness of different types of reduction interventions (e.g. pharmacist-led versus general practitioner-led, educational versus audit and feedback) for reducing overall anticholinergic burden. • To establish optimal duration of anticholinergic reduction interventions, sustainability, and lessons learnt for upscaling • To compare results according to differing anticholinergic scales used in medication reduction intervention trials • To assess the efficacy of anticholinergic medication reduction interventions for improving other clinical outcomes, including mortality, quality of life, clinical global impression, physical function, institutionalisation, falls, cardiovascular diseases, and neurobehavioral outcomes. SEARCH METHODS We searched CENTRAL on 22 December 2022, and we searched MEDLINE, Embase, and three other databases from inception to 1 November 2022. SELECTION CRITERIA We included randomised controlled trials (RCTs) of interventions that aimed to reduce anticholinergic burden in older people and that investigated cognitive outcomes. DATA COLLECTION AND ANALYSIS Two review authors independently assessed studies for inclusion, extracted data, and assessed the risk of bias of included studies. The data were not suitable for meta-analysis, so we summarised them narratively. We used GRADE methods to rate our confidence in the review results. MAIN RESULTS We included three trials with a total of 299 participants. All three trials were conducted in a cognitively mixed population (some cognitively healthy participants, some participants with dementia). Outcomes were assessed after one to three months. One trial reported significantly improved performance on the Digit Symbol Substitution Test (DSST) in the intervention group (treatment difference 0.70, 95% confidence interval (CI) 0.11 to 1.30), although there was no difference between the groups in the proportion of participants with reduced anticholinergic burden. Two trials successfully reduced anticholinergic burden in the intervention group. Of these, one reported no significant difference between the intervention versus control in terms of their effect on cognitive performance measured by the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) immediate recall (mean between-group difference 0.54, 95% CI -0.91 to 2.05), CERAD delayed recall (mean between-group difference -0.23, 95% CI-0.85 to 0.38), CERAD recognition (mean between-group difference 0.77, 95% CI -0.39 to 1.94), and Mini-Mental State Examination (mean between-group difference 0.39, 95% CI -0.96 to 1.75). The other trial reported a significant correlation between anticholinergic burden and a test of working memory after the intervention (which suggested reducing the burden improved performance), but reported no effect on multiple other cognitive measures. In GRADE terms, the results were of very low certainty. There were no reported between-group differences for any other clinical outcome we investigated. It was not possible to investigate differences according to type of reduction intervention or type of anticholinergic scale, to measure the sustainability of interventions, or to establish lessons learnt for upscaling. No trials investigated safety outcomes. AUTHORS' CONCLUSIONS There is insufficient evidence to reach any conclusions on the effects of anticholinergic burden reduction interventions on cognitive outcomes in older adults with or without prior cognitive impairment. The evidence from RCTs was of very low certainty so cannot support or refute the hypothesis that actively reducing or stopping prescription of medications with anticholinergic properties can improve cognitive outcomes in older people. There is no evidence from RCTs that anticholinergic burden reduction interventions improve other clinical outcomes such as mortality, quality of life, clinical global impression, physical function, institutionalisation, falls, cardiovascular diseases, or neurobehavioral outcomes. Larger RCTs investigating long-term outcomes are needed. Future RCTs should also investigate potential benefits of anticholinergic reduction interventions in cognitively healthy populations and cognitively impaired populations separately.
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Mechanisms affecting the gut of preterm infants in enteral feeding trials: a nested cohort within a randomised controlled trial of lactoferrin.
Young, G, Berrington, JE, Cummings, S, Dorling, J, Ewer, AK, Frau, A, Lett, L, Probert, C, Juszczak, E, Kirby, J, et al
Archives of disease in childhood. Fetal and neonatal edition. 2023;(3):272-279
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Abstract
OBJECTIVE To determine the impact of supplemental bovine lactoferrin on the gut microbiome and metabolome of preterm infants. DESIGN Cohort study nested within a randomised controlled trial (RCT). Infants across different trial arms were matched on several clinical variables. Bacteria and metabolite compositions of longitudinal stool and urine samples were analysed to investigate the impact of lactoferrin supplementation. SETTING Thirteen UK hospitals participating in a RCT of lactoferrin. PATIENTS 479 infants born <32 weeks' gestation between June 2016 and September 2017. RESULTS 10 990 stool and 22 341 urine samples were collected. Analyses of gut microbiome (1304 stools, 201 infants), metabolites (171 stools, 83 infants; 225 urines, 90 infants) and volatile organic compounds (314 stools, 117 infants) were performed. Gut microbiome Shannon diversity at 34 weeks corrected age was not significantly different between infants in the lactoferrin (mean=1.24) or placebo (mean=1.06) groups (p=0.11). Lactoferrin receipt explained less than 1% variance in microbiome compositions between groups. Metabolomic analysis identified six discriminative features between trial groups. Hospital site (16%) and postnatal age (6%) explained the greatest variation in microbiome composition. CONCLUSIONS This multiomic study identified minimal impacts of lactoferrin but much larger impacts of hospital site and postnatal age. This may be due to the specific lactoferrin product used, but more likely supports the findings of the RCT in which this study was nested, which showed no impact of lactoferrin on reducing rates of sepsis. Multisite mechanistic studies nested within RCTs are feasible and help inform trial interpretation and future trial design.
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Effects of environmental impact and nutrition labelling on food purchasing: An experimental online supermarket study.
Potter, C, Pechey, R, Cook, B, Bateman, P, Stewart, C, Frie, K, Clark, M, Piernas, C, Rayner, M, Jebb, SA
Appetite. 2023;:106312
Abstract
Nutrition labels and ecolabels can support consumers to make healthier and more sustainable choices, and the former is now widespread. But there is no information on the impact of ecolabels in the presence of nutrition labels. The aims of this study were primarily to examine whether (1) ecolabels are effective at promoting sustainable purchasing behaviour if presented alongside nutrition labels; (2) and secondarily, whether nutrition labels are effective at promoting healthier purchasing if presented alongside ecolabels. Participants (N = 2730) visited an experimental online supermarket platform, and were randomised to see products with (1) environmental impact labels only; (2) nutrition (NutriScore) labels only; (3) both environmental and nutrition labels; (4) no labels. Linear regressions compared the mean environmental impact scores (EIS; primary outcome) and health scores of products in participants' shopping baskets across each condition. Compared to control (no labels) there were significant reductions in the EIS when environmental impact labels were presented: Alone (-1.3, 95%CI: -2.3 to -0.4) or With nutrition labels (-2.0, 95%CI: -2.9 to -1.0), with no evidence of differences in effectiveness between these two conditions. There was no evidence of an impact of nutrition labels on either the EIS or the healthiness of purchases, both when nutrition labels were shown alone and when ecolabels were also present. Environmental impact labels may be effective at encouraging more sustainable purchases alone or when used alongside nutrition labels. This adds to the evidence base on the feasibility and effectiveness of environmental impact labelling as an important measure to change dietary behaviour to improve planetary health.
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Effects of a mediterranean diet on the gut microbiota and microbial metabolites: A systematic review of randomized controlled trials and observational studies.
Kimble, R, Gouinguenet, P, Ashor, A, Stewart, C, Deighton, K, Matu, J, Griffiths, A, Malcomson, FC, Joel, A, Houghton, D, et al
Critical reviews in food science and nutrition. 2023;(27):8698-8719
Abstract
Consumption of the Mediterranean dietary pattern (MedDiet) is associated with reduced risk of numerous non-communicable diseases. Modulation of the composition and metabolism of the gut microbiota represents a potential mechanism through which the MedDiet elicits these effects. We conducted a systematic literature search (Prospero registration: CRD42020168977) using PubMed, The Cochrane Library, MEDLINE, SPORTDiscuss, Scopus and CINAHL databases for randomized controlled trials (RCTs) and observational studies exploring the impact of a MedDiet on gut microbiota composition (i.e., relative abundance of bacteria or diversity metrics) and metabolites (e.g., short chain fatty acids). Seventeen RCTs and 17 observational studies were eligible for inclusion in this review. Risk of bias across the studies was mixed but mainly identified as low and unclear. Overall, RCTs and observational studies provided no clear evidence of a consistent effect of a MedDiet on composition or metabolism of the gut microbiota. These findings may be related to the diverse methods across studies (e.g., MedDiet classification and analytical techniques), cohort characteristics, and variable quality of studies. Further, well-designed studies are warranted to advance understanding of the potential effects of the MedDiet using more detailed examination of microbiota and microbial metabolites with reference to emerging characteristics of a healthy gut microbiome.
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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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Identifying effective characteristics of behavioral weight management interventions for people with serious mental illness: A systematic review with a qualitative comparative analysis.
Lee, C, Piernas, C, Stewart, C, Michalopoulou, M, Hajzadeh, A, Edwards, R, Aveyard, P, Waite, F
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2022;(1):e13355
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Abstract
People with serious mental illness (SMI) have identified barriers to engaging in behavioral weight management interventions (BWMIs). We assessed whether BWMIs that addressed these barriers were more effective. First, we systematically reviewed qualitative literature and used a thematic analysis to identify the characteristics of BWMIs that promote engagement for adults with SMI. Second, we systematically reviewed randomized controlled trials (RCTs) of BWMIs in adults with SMI. Data on the characteristics that promoted engagement and weight outcomes were extracted. We then used a crisp-set qualitative comparative analysis (CsQCA) to identify which characteristics were associated with weight loss. For the qualitative review, 20 studies in 515 people with SMI were analyzed and nine characteristics were reported to promote engagement in BWMIs. For the systematic review, 34 RCTs testing 36 interventions in 4305 participants were included. The active interventions resulted in more weight loss (mean = -4.37 to +1 kg at 6 weeks to 18 months follow-up) compared with controls (-1.64 to +3.08 kg). The CsQCA showed BWMIs that offered regular contact, tools to support enactment, and tailored materials were associated with effectiveness. As these are all supplementary strategies, it may be possible to augment BWMIs available for the general population to engage people with SMI.
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A dynamic social norm messaging intervention to reduce meat consumption: A randomized cross-over trial in retail store restaurants.
Çoker, EN, Pechey, R, Frie, K, Jebb, SA, Stewart, C, Higgs, S, Cook, B
Appetite. 2022;:105824
Abstract
Perceptions of social norms around eating behavior can influence food choices. Communicating information about how others are changing their eating behavior over time (dynamic descriptive social norms) may motivate individuals to change their own food selection and consumption. Following a four-week baseline period, 22 in-store restaurants of a major retail chain across the UK were randomized to display a dynamic descriptive social norm message intended to motivate a shift from meat-to plant-based meals either during the first two, or last two weeks of the four-week study period. A linear regression model showed there was no evidence of an effect of the intervention (β = -0.022, p = .978, 95% CIs: -1.63, 1.58) on the percentage sales of meat- vs plant-based dishes. Fidelity checks indicated that adherence to the intervention procedure was often low, with inconsistencies in the placement and display of the intervention message. In four stores with high fidelity the estimated impact of the intervention was not materially different. The lack of apparent effectiveness of the intervention may reflect poor efficacy of the intervention or limitations in its implementation in a complex food purchasing environment. The challenges highlighted by this study should be considered in future design and evaluation of field trials in real-world settings.
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Measurement Properties of Smartphone Approaches to Assess Diet, Alcohol Use, and Tobacco Use: Systematic Review.
Thornton, L, Osman, B, Champion, K, Green, O, Wescott, AB, Gardner, LA, Stewart, C, Visontay, R, Whife, J, Parmenter, B, et al
JMIR mHealth and uHealth. 2022;(2):e27337
Abstract
BACKGROUND Poor diet, alcohol use, and tobacco smoking have been identified as strong determinants of chronic diseases, such as cardiovascular disease, diabetes, and cancer. Smartphones have the potential to provide a real-time, pervasive, unobtrusive, and cost-effective way to measure these health behaviors and deliver instant feedback to users. Despite this, the validity of using smartphones to measure these behaviors is largely unknown. OBJECTIVE The aim of our review is to identify existing smartphone-based approaches to measure these health behaviors and critically appraise the quality of their measurement properties. METHODS We conducted a systematic search of the Ovid MEDLINE, Embase (Elsevier), Cochrane Library (Wiley), PsycINFO (EBSCOhost), CINAHL (EBSCOHost), Web of Science (Clarivate), SPORTDiscus (EBSCOhost), and IEEE Xplore Digital Library databases in March 2020. Articles that were written in English; reported measuring diet, alcohol use, or tobacco use via a smartphone; and reported on at least one measurement property (eg, validity, reliability, and responsiveness) were eligible. The methodological quality of the included studies was assessed using the Consensus-Based Standards for the Selection of Health Measurement Instruments Risk of Bias checklist. Outcomes were summarized in a narrative synthesis. This systematic review was registered with PROSPERO, identifier CRD42019122242. RESULTS Of 12,261 records, 72 studies describing the measurement properties of smartphone-based approaches to measure diet (48/72, 67%), alcohol use (16/72, 22%), and tobacco use (8/72, 11%) were identified and included in this review. Across the health behaviors, 18 different measurement techniques were used in smartphones. The measurement properties most commonly examined were construct validity, measurement error, and criterion validity. The results varied by behavior and measurement approach, and the methodological quality of the studies varied widely. Most studies investigating the measurement of diet and alcohol received very good or adequate methodological quality ratings, that is, 73% (35/48) and 69% (11/16), respectively, whereas only 13% (1/8) investigating the measurement of tobacco use received a very good or adequate rating. CONCLUSIONS This review is the first to provide evidence regarding the different types of smartphone-based approaches currently used to measure key behavioral risk factors for chronic diseases (diet, alcohol use, and tobacco use) and the quality of their measurement properties. A total of 19 measurement techniques were identified, most of which assessed dietary behaviors (48/72, 67%). Some evidence exists to support the reliability and validity of using smartphones to assess these behaviors; however, the results varied by behavior and measurement approach. The methodological quality of the included studies also varied. Overall, more high-quality studies validating smartphone-based approaches against criterion measures are needed. Further research investigating the use of smartphones to assess alcohol and tobacco use and objective measurement approaches is also needed. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-https://doi.org/10.1186/s13643-020-01375-w.
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Testing the effectiveness of ecolabels to reduce the environmental impact of food purchases in worksite cafeterias: A randomised controlled trial.
Pechey, R, Bateman, PA, Cook, B, Potter, C, Clark, M, Stewart, C, Piernas, C, Jebb, SA
Appetite. 2022;:106277
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Microbiome and paediatric gut diseases.
Gerasimidis, K, Gkikas, K, Stewart, C, Neelis, E, Svolos, V
Archives of disease in childhood. 2022;(9):784-789
Abstract
In the human gut resides a vast community of microorganisms which perform critical functions for the maintenance of whole body homeostasis. Changes in the composition and function of this community, termed microbiome, are believed to provoke disease onset, including non-communicable diseases. In this review, we debate the current evidence on the role of the gut microbiome in the pathogenesis, outcomes and management of paediatric gut disease. We conclude that even though the gut microbiome is altered in paediatric inflammatory bowel disease, coeliac disease, intestinal failure, necrotising enterocolitis and irritable bowel syndrome, there are currently very few implications for unravelling disease pathogenesis or guiding clinical practice. In the future, the gut microbiome may aid in disease differential diagnosis and prediction of clinical outcomes, and comprise a target for therapeutic interventions.