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Association between urea trajectory and protein dose in critically ill adults: a secondary exploratory analysis of the effort protein trial (RE-EFFORT).
Haines, RW, Prowle, JR, Day, A, Bear, DE, Heyland, DK, Puthucheary, Z
Critical care (London, England). 2024;(1):24
Abstract
BACKGROUND Delivering higher doses of protein to mechanically ventilated critically ill patients did not improve patient outcomes and may have caused harm. Longitudinal urea measurements could provide additional information about the treatment effect of higher protein doses. We hypothesised that higher urea values over time could explain the potential harmful treatment effects of higher doses of protein. METHODS We conducted a reanalysis of a randomised controlled trial of higher protein doses in critical illness (EFFORT Protein). We applied Bayesian joint models to estimate the strength of association of urea with 30-day survival and understand the treatment effect of higher protein doses. RESULTS Of the 1301 patients included in EFFORT Protein, 1277 were included in this analysis. There were 344 deaths at 30 days post-randomisation. By day 6, median urea was 2.1 mmol/L higher in the high protein group (95% CI 1.1-3.2), increasing to 3.0 mmol/L (95% CI 1.3-4.7) by day 12. A twofold rise in urea was associated with an increased risk of death at 30 days (hazard ratio 1.34, 95% credible interval 1.21-1.48), following adjustment of baseline characteristics including age, illness severity, renal replacement therapy, and presence of AKI. This association persisted over the duration of 30-day follow-up and in models adjusting for evolution of organ failure over time. CONCLUSIONS The increased risk of death in patients randomised to a higher protein dose in the EFFORT Protein trial was estimated to be mediated by increased urea cycle activity, of which serum urea is a biological signature. Serum urea should be taken into consideration when initiating and continuing protein delivery in critically ill patients. CLINICALTRIALS gov Identifier: NCT03160547 (2017-05-17).
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Creatine supplementation in the pediatric and adolescent athlete-- A literature review.
Metzger, GA, Minneci, PM, Gehred, A, Day, A, Klingele, KE
Journal of orthopaedics. 2023;:73-78
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Abstract
BACKGROUND An increase in intra-muscular creatine through supplementation has been proposed as a strategy for improving muscle performance and recovery, with studies showing some benefit for adult athletes who rely on short, explosive movements. We reviewed and summarized the current literature on creatine supplementation in a pediatric and adolescent population. METHODS The databases PubMed and EMBASE were queried to identity articles related to the use of creatine supplementation in a healthy pediatric and adolescent population according to the guidelines established by PRISMA. The abstracts of all articles were reviewed to determine relevancy, with those meeting the pre-defined criteria included in the final review. RESULTS A combined total of 9393 articles were identified. Following application of filters and review of abstracts, 13 articles were found to meet criteria and were included in the final review. There was a total of 268 subjects across all studies, with mean age ranging from 11.5 to 18.2 years. More than 75% of the studies were randomized-controlled trials, and 85% involved either soccer players or swimmers. The overall quality of the studies was poor, and there were no consistent findings regarding creatine supplementation and improvements in athletic performance. No studies were designed to address the topic of safety. CONCLUSIONS There is a gap in the study of the safety and efficacy of creatine supplementation in adolescents. Additional studies are needed to evaluate the effects of alterations in muscle composition on the growth, development, and performance of the developing athlete. Orthopedic providers should counsel their pediatric and adolescent patients on the current limitations in trying to assess the true risk and benefit of creatine supplementation for the aspiring athlete. LEVEL OF EVIDENCE Review, III.
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Catabolism in Critical Illness: A Reanalysis of the REducing Deaths due to OXidative Stress (REDOXS) Trial.
Haines, RW, Fowler, AJ, Wan, YI, Flower, L, Heyland, DK, Day, A, Pearse, RM, Prowle, JR, Puthucheary, Z
Critical care medicine. 2022;(7):1072-1082
Abstract
OBJECTIVES Ongoing risk of death and poor functional outcomes are important consequences of prolonged critical illness. Characterizing the catabolic phenotype of prolonged critical illness could illuminate biological processes and inform strategies to attenuate catabolism. We aimed to examine if urea-to-creatinine ratio, a catabolic signature of prolonged critical illness, was associated with mortality after the first week of ICU stay. DESIGN Reanalysis of multicenter randomized trial of glutamine supplementation in critical illness (REducing Deaths due to OXidative Stress [REDOXS]). SETTING Multiple adult ICUs. PATIENTS Adult patients admitted to ICU with two or more organ failures related to their acute illness and surviving to day 7. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS The association between time-varying urea-to-creatinine ratio and 30-day mortality was tested using Bayesian joint models adjusted for prespecified-covariates (age, kidney replacement therapy, baseline Sequential Organ Failure Assessment, dietary protein [g/kg/d], kidney dysfunction, and glutamine-randomization). From 1,021 patients surviving to day 7, 166 (16.3%) died by day 30. After adjustment in a joint model, a higher time-varying urea-to-creatinine ratio was associated with increased mortality (hazard ratio [HR], 2.15; 95% credible interval, 1.66-2.82, for a two-fold greater urea-to-creatinine ratio). This association persisted throughout the 30-day follow-up. Mediation analysis was performed to explore urea-to-creatinine ratio as a mediator-variable for the increased risk of death reported in REDOXS when randomized to glutamine, an exogenous nitrogen load. Urea-to-creatinine ratio closest to day 7 was estimated to mediate the risk of death associated with randomization to glutamine supplementation (HR, 1.20; 95% CI, 1.04-1.38; p = 0.014), with no evidence of a direct effect of glutamine (HR, 0.90; 95% CI, 0.62-1.30; p = 0.566). CONCLUSIONS The catabolic phenotype measured by increased urea-to-creatinine ratio is associated with increased risk of death during prolonged ICU stay and signals the deleterious effects of glutamine administration in the REDOXS study. Urea-to-creatinine ratio is a promising catabolic signature and potential interventional target.
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Diallyl Sulfide Attenuation of Carcinogenesis in Mammary Epithelial Cells through the Inhibition of ROS Formation, and DNA Strand Breaks.
Darling-Reed, SF, Nkrumah-Elie, Y, Ferguson, DT, Flores-Rozas, H, Mendonca, P, Messeha, S, Hudson, A, Badisa, RB, Tilghman, SL, Womble, T, et al
Biomolecules. 2021;(9)
Abstract
Garlic has long been used medicinally for many diseases, including cancer. One of the active garlic components is diallyl sulfide (DAS), which prevents carcinogenesis and reduces the incidence rate of several cancers. In this study, non-cancerous MCF-10A cells were used as a model to investigate the effect of DAS on Benzo (a)pyrene (BaP)-induced cellular carcinogenesis. The cells were evaluated based on changes in proliferation, cell cycle arrest, the formation of peroxides, 8-hydroxy-2-deoxyguanosine (8-OHdG) levels, the generation of DNA strand breaks, and DNA Polymerase β (Pol β) expression. The results obtained indicate that when co-treated with BaP, DAS inhibited BaP-induced cell proliferation (p < 0.05) to levels similar to the negative control. BaP treatment results in a two-fold increase in the accumulation of cells in the G2/M-phase of the cell cycle, which is restored to baseline levels, similar to untreated cells and vehicle-treated cells, when pretreated with 6 μM and 60 μM DAS, respectively. Co-treatment with DAS (60 μM and 600 μM) inhibited BaP-induced reactive oxygen species (ROS) formation by 132% and 133%, respectively, as determined by the accumulation of H2O2 in the extracellular medium and an increase in 8-OHdG levels of treated cells. All DAS concentrations inhibited BaP-induced DNA strand breaks through co-treatment and pre-treatment methods at all time points evaluated. Co-Treatment with 60 μM DAS increased DNA Pol β expression in response to BaP-induced lipid peroxidation and oxidative DNA damage. These results indicate that DAS effectively inhibited BaP-induced cell proliferation, cell cycle transitions, ROS, and DNA damage in an MCF-10A cell line. These results provide more experimental evidence for garlic's antitumor abilities and corroborate many epidemiological studies regarding the association between the increased intake of garlic and the reduced risk of several types of cancer.
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Efficacy and safety of low and very low carbohydrate diets for type 2 diabetes remission: systematic review and meta-analysis of published and unpublished randomized trial data.
Goldenberg, JZ, Day, A, Brinkworth, GD, Sato, J, Yamada, S, Jönsson, T, Beardsley, J, Johnson, JA, Thabane, L, Johnston, BC
BMJ (Clinical research ed.). 2021;372:m4743
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Plain language summary
Diet modification has long been recognised as a component for the treatment of diabetes. Diets low in carbohydrates have been extensively researched, as a diet for those with Type 2 Diabetes (T2D). This systematic review and meta-analysis aimed to determine the effect of low carbohydrate diets on T2D. The systematic review found 23 studies, including 1357 individuals, investigating the role of low carbohydrate diets on T2D outcomes. Low carbohydrate diet was defined as less than 130g of carbohydrate (less than 26% of calories from carbohydrate) for at least 12 weeks. Results reported at 6 months, found low carbohydrate diets were more effective than a normal diet at achieving diabetes remission. However, this effect diminished at 12 months, although longer term improvements were seen in blood lipids, weight loss and measures of prediabetes. It was concluded that individuals with T2D, eating a low carbohydrate diet for 6 months may reverse the disease. This study could be used by healthcare professionals to recommend a short-term low carbohydrate diet to individuals with T2D, to improve their chance of going into remission.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Type 2 diabetes remains a significant and worsening problem worldwide, despite many pharmaceutical developments and a global emphasis on glycemic control.
- This review highlights structured LCDs as a worthwhile option for the management and treatment of diabetes, providing an opportunity for Nutritional Therapy Practitioners to support clients in adopting evidence-informed, modifiable dietary and lifestyle changes for Type Two Diabetes.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
- Type 2 diabetes is the most common form of diabetes, accounting for 90-95% of cases.
- Previous randomised trials assessed low carbohydrate diets (LCDs) (<26-45% of daily calories from carbohydrate) as encouraging to improve blood glucose control and outcomes of type 2 diabetes but did not systematically assessed remission of diabetes using low carbohydrate diets (LCDs) and very low carbohydrate diets (VLCDs) for people with type 2 diabetes.
- Systematic reviews (SR) and meta-analyses represent the most valuable, reliable, and objective tool to summarise evidence from primary studies.
- This SR assessed 23 randomised controlled trials comparing LCDs with mostly low fat control diets in individuals / subjects / participants with type 2 diabetes. LCDs were defined as diets with less than 130 g/day or less than 26% of calories from carbohydrates, based on 2000 kcal/day. The authors used the Cochrane Risk of Bias tool 2.0 (RoB 2) to assess methodological quality of evidence, GRADE to assess the certainty of evidence
- On the basis of assessment of moderate to low certainty evidence, individuals / subjects / participants adhering to a LCD for six months may experience remission of type 2 diabetes without adverse consequences.
- Primary outcomes of interest were remission of type 2 diabetes (dichotomously defined as HbA1c <6.5% or fasting glucose <7.0 mmol/L), with or without the use of diabetes medication.
- Eight studies reported on remission of diabetes at six months. Pooled analysis showed that when remission was defined by an HbA1c level below 6.5% independent of medication use, LCDs increased remissions by an additional 32 per 100 patients followed (risk difference 0.32, 95% confidence interval 0.17 to 0.47; 8 studies, n=264; GRADE=moderate)
- When remission was defined by an HbA1c level below 6.5% and the absence of diabetes medication, LCDs increased remissions at a lower rate (risk difference 0.05, –0.05 to 0.14; 5 studies, n=199; GRADE=low)
- Additional primary outcomes were weight loss, HbA1c:
- 18 studies reported on Weight loss results (mean difference –3.46, 95% confidence interval –5.25 to –1.67; n=882 (note that positive results not sustained at 12 mo)
- Seventeen studies reported on HbA1c levels at six months, LCDs achieved greater reductions in HbA1c than did control diets (mean difference –0.47%, –0.60 to –0.34; n=747
- Limitations of study: 1) the definition of remission of diabetes, 2) Self-reported dietary intake data are prone to measurement error, particularly in dietary trials in which participants are not blinded
- This SR was funded in part by Texas A&M University.
- The authors declared no conflicts of interest.
Clinical practice applications:
The Authors highlight LCD diets incorporating carbohydrate of less than 130 g/day or less than 26% of calories (based on 2000 kcal/day) may be a safe strategy to help individuals with type 2 diabetes achieve weight loss and better blood glucose control over a six-month period. Results may not be sustained at 12 months.
Considerations for future research:
- The definition of diabetes remission needs clarification, especially with regard to threshold concentrations of Hb1Ac or fasting glucose and the use of diabetes medication.
- Safety concerns have been raised with LCDs. Although no significant or clinically important increase in total or serious adverse events was identified in this SR, these outcomes should be reported in future trials to confirm the certainty of evidence for safety.
- The Authors suggest long term, well designed, calorie controlled randomised trials are needed to determine the effects of LCD on sustained weight loss and remission of diabetes.
- Larger treatment effects for LCDs in shorter term trials (3 to <6 months), may be trialed as an effect modifier
Abstract
OBJECTIVE To determine the efficacy and safety of low carbohydrate diets (LCDs) and very low carbohydrate diets (VLCDs) for people with type 2 diabetes. DESIGN Systematic review and meta-analysis. DATA SOURCES Searches of CENTRAL, Medline, Embase, CINAHL, CAB, and grey literature sources from inception to 25 August 2020. STUDY SELECTION Randomized clinical trials evaluating LCDs (<130 g/day or <26% of a 2000 kcal/day diet) and VLCDs (<10% calories from carbohydrates) for at least 12 weeks in adults with type 2 diabetes were eligible. DATA EXTRACTION Primary outcomes were remission of diabetes (HbA1c <6.5% or fasting glucose <7.0 mmol/L, with or without the use of diabetes medication), weight loss, HbA1c, fasting glucose, and adverse events. Secondary outcomes included health related quality of life and biochemical laboratory data. All articles and outcomes were independently screened, extracted, and assessed for risk of bias and GRADE certainty of evidence at six and 12 month follow-up. Risk estimates and 95% confidence intervals were calculated using random effects meta-analysis. Outcomes were assessed according to a priori determined minimal important differences to determine clinical importance, and heterogeneity was investigated on the basis of risk of bias and seven a priori subgroups. Any subgroup effects with a statistically significant test of interaction were subjected to a five point credibility checklist. RESULTS Searches identified 14 759 citations yielding 23 trials (1357 participants), and 40.6% of outcomes were judged to be at low risk of bias. At six months, compared with control diets, LCDs achieved higher rates of diabetes remission (defined as HbA1c <6.5%) (76/133 (57%) v 41/131 (31%); risk difference 0.32, 95% confidence interval 0.17 to 0.47; 8 studies, n=264, I2=58%). Conversely, smaller, non-significant effect sizes occurred when a remission definition of HbA1c <6.5% without medication was used. Subgroup assessments determined as meeting credibility criteria indicated that remission with LCDs markedly decreased in studies that included patients using insulin. At 12 months, data on remission were sparse, ranging from a small effect to a trivial increased risk of diabetes. Large clinically important improvements were seen in weight loss, triglycerides, and insulin sensitivity at six months, which diminished at 12 months. On the basis of subgroup assessments deemed credible, VLCDs were less effective than less restrictive LCDs for weight loss at six months. However, this effect was explained by diet adherence. That is, among highly adherent patients on VLCDs, a clinically important reduction in weight was seen compared with studies with less adherent patients on VLCDs. Participants experienced no significant difference in quality of life at six months but did experience clinically important, but not statistically significant, worsening of quality of life and low density lipoprotein cholesterol at 12 months. Otherwise, no significant or clinically important between group differences were found in terms of adverse events or blood lipids at six and 12 months. CONCLUSIONS On the basis of moderate to low certainty evidence, patients adhering to an LCD for six months may experience remission of diabetes without adverse consequences. Limitations include continued debate around what constitutes remission of diabetes, as well as the efficacy, safety, and dietary satisfaction of longer term LCDs. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42020161795.
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Immunotherapy to improve pregnancy outcome in women with abnormal natural killer cell levels/activity and recurrent miscarriage or implantation failure: A systematic review and meta-analysis.
Woon, EV, Day, A, Bracewell-Milnes, T, Male, V, Johnson, M
Journal of reproductive immunology. 2020;:103189
Abstract
There is a trend towards offering immunotherapy to women with unexplained reproductive failure based on abnormal Natural Killer (NK) cell levels. Previous systematic reviews evaluating immunotherapy usage have not focused on women with abnormal level of NK cells. To address the gap in literature, this systematic review aims to evaluate the efficacy of immunotherapy to improve pregnancy outcome in women with recurrent miscarriage (RM) or implantation failure (RIF) specifically selected based on abnormal levels and/or activity of NK cells. Six databases were searched for peer-reviewed studies following PRISMA guidelines. Risk of bias assessment was conducted using RoB2 for randomized controlled trials (RCT) and ROBINS-I for non-RCT. Of 1025 studies identified, seven studies on intravenous immunoglobulin (IVIG) (four), prednisolone (one), etanercept (one) and intralipid (one) were included. Meta-analysis of the non-RCT IVIG studies (557 participants; 312 intervention, 245 controls) showed livebirth in favour of intervention (RR 2.57; 95 % CI = 1.79-3.69; p < 0.05), however there were significant heterogeneity (I2 = 62 %) and moderate to severe risk of bias in these studies. Individual RCTs reported improved livebirth outcome in etanercept, intralipid and prednisolone and this was significant in the former two (p < 0.05). In conclusion, there may be some benefit of immunotherapy, but paucity of high quality evidence means that it is not possible to support the use of immunotherapy even when selected based on abnormal NK cell level/activity. Further research with application of scientifically validated immunological biomarkers in well-planned large scale RCTs will determine whether immunotherapy is beneficial in this subpopulation of women.
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Nutrition and Exercise in Critical Illness Trial (NEXIS Trial): a protocol of a multicentred, randomised controlled trial of combined cycle ergometry and amino acid supplementation commenced early during critical illness.
Heyland, DK, Day, A, Clarke, GJ, Hough, CT, Files, DC, Mourtzakis, M, Deutz, N, Needham, DM, Stapleton, R
BMJ open. 2019;(7):e027893
Abstract
INTRODUCTION Survivors of critical illness often experience significant morbidities, including muscle weakness and impairments in physical functioning. This muscle weakness is associated with longer duration mechanical ventilation, greater hospital costs and increased postdischarge impairments in physical function, quality of life and survival. Compared with standard of care, the benefits of greater protein intake combined with structured exercise started early after the onset of critical illness remain uncertain. However, the combination of protein supplementation and exercise in other populations has demonstrated positive effects on strength and function. In the present study, we will evaluate the effects of a combination of early implementation of intravenous amino acid supplementation and in-bed cycle ergometry exercise versus a 'usual care' control group in patients with acute respiratory failure requiring mechanical ventilation in an intensive care unit (ICU). METHODS AND ANALYSIS In this multicentre, assessor-blinded, randomised controlled trial, we will randomise 142 patients in a 1:1 ratio to usual care (which commonly consists of minimal exercise and under-achievement of guideline-recommended caloric and protein intake goals) versus a combined intravenous amino acid supplementation and in-bed cycle ergometery exercise intervention. We hypothesise that this novel combined intervention will (1) improve physical functioning at hospital discharge; (2) reduce muscle wasting with improved amino acid metabolism and protein synthesis in-hospital and (3) improve patient-reported outcomes and healthcare resource utilisation at 6 months after enrolment. Key cointerventions will be standardised. In-hospital outcome assessments will be conducted at baseline, ICU discharge and hospital discharge. An intent-to-treat analysis will be used to analyse all data with additional per-protocol analyses. ETHICS AND DISSEMINATION The trial received ethics approval at each institution and enrolment has begun. These results will inform both clinical practice and future research in the area. We plan to disseminate trial results in peer-reviewed journals, at national and international conferences, and via nutritional and rehabilitation-focused electronic education and knowledge translation platforms. TRIAL REGISTRATION NUMBER NCT03021902; Pre-results.
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A Cell Wall Proteome and Targeted Cell Wall Analyses Provide Novel Information on Hemicellulose Metabolism in Flax.
Chabi, M, Goulas, E, Leclercq, CC, de Waele, I, Rihouey, C, Cenci, U, Day, A, Blervacq, AS, Neutelings, G, Duponchel, L, et al
Molecular & cellular proteomics : MCP. 2017;(9):1634-1651
Abstract
Experimentally-generated (nanoLC-MS/MS) proteomic analyses of four different flax organs/tissues (inner-stem, outer-stem, leaves and roots) enriched in proteins from 3 different sub-compartments (soluble-, membrane-, and cell wall-proteins) was combined with publically available data on flax seed and whole-stem proteins to generate a flax protein database containing 2996 nonredundant total proteins. Subsequent multiple analyses (MapMan, CAZy, WallProtDB and expert curation) of this database were then used to identify a flax cell wall proteome consisting of 456 nonredundant proteins localized in the cell wall and/or associated with cell wall biosynthesis, remodeling and other cell wall related processes. Examination of the proteins present in different flax organs/tissues provided a detailed overview of cell wall metabolism and highlighted the importance of hemicellulose and pectin remodeling in stem tissues. Phylogenetic analyses of proteins in the cell wall proteome revealed an important paralogy in the class IIIA xyloglucan endo-transglycosylase/hydrolase (XTH) family associated with xyloglucan endo-hydrolase activity.Immunolocalisation, FT-IR microspectroscopy, and enzymatic fingerprinting indicated that flax fiber primary/S1 cell walls contained xyloglucans with typical substituted side chains as well as glucuronoxylans in much lower quantities. These results suggest a likely central role of xyloglucans and endotransglucosylase/hydrolase activity in flax fiber formation and cell wall remodeling processes.
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Elevated ghrelin predicts food intake during experimental sleep restriction.
Broussard, JL, Kilkus, JM, Delebecque, F, Abraham, V, Day, A, Whitmore, HR, Tasali, E
Obesity (Silver Spring, Md.). 2016;(1):132-8
Abstract
OBJECTIVE Sleep curtailment has been linked to obesity, but underlying mechanisms remain to be elucidated. This study assessed whether sleep restriction alters 24-h profiles of appetite-regulating hormones ghrelin, leptin, and pancreatic polypeptide during a standardized diet and whether these hormonal alterations predict food intake during ad libitum feeding. METHODS Nineteen healthy, lean men were studied under normal sleep and sleep restriction in a randomized crossover design. Blood samples were collected for 24 h during standardized meals. Subsequently, participants had an ad libitum feeding opportunity (buffet meals and snacks) and caloric intake was measured. RESULTS Ghrelin levels were increased after sleep restriction as compared with normal sleep (P < 0.01). Overall, sleep restriction did not alter leptin or pancreatic polypeptide profiles. Sleep restriction was associated with an increase in total calories from snacks by 328 ± 140 kcal (P = 0.03), primarily from carbohydrates (P = 0.02). The increase in evening ghrelin during sleep restriction was correlated with higher consumption of calories from sweets (r = 0.48, P = 0.04). CONCLUSIONS Sleep restriction as compared with normal sleep significantly increases ghrelin levels. The increase in ghrelin is associated with higher consumption of calories. Elevated ghrelin may be a mechanism by which sleep loss leads to increased food intake and the development of obesity.
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Anti-inflammatory therapy after selective laser trabeculoplasty: a randomized, double-masked, placebo-controlled clinical trial.
Jinapriya, D, D'Souza, M, Hollands, H, El-Defrawy, SR, Irrcher, I, Smallman, D, Farmer, JP, Cheung, J, Urton, T, Day, A, et al
Ophthalmology. 2014;(12):2356-61
Abstract
PURPOSE To investigate the effect of anti-inflammatory therapy on selective laser trabeculoplasty (SLT) outcomes. DESIGN Randomized, double-masked, placebo-controlled trial. PARTICIPANTS Patients with primary open-angle or pseudo-exfoliation glaucoma. METHODS Patients undergoing SLT were randomized to receive placebo (artificial tears), prednisolone acetate 1%, or ketorolac tromethamine 0.5% eye drops 4 times per day for 5 days commencing immediately after SLT. MAIN OUTCOME MEASURES Change in intraocular pressure (IOP) from baseline to the 1-month post-SLT visit. RESULTS Mean change in IOP at the 1-month primary outcome time point, as well as all other time points, was not significantly different among groups (P = 0.99). Likewise, a repeated-measures, mixed-effects model did not find significant differences in IOP outcome at the 1-month time point (P = 0.95). The IOP was reduced in all groups at the 1-month post-SLT time point and all other time points, and no significant differences were found between groups using separate unadjusted cross-sectional analyses of variance (P > 0.15 for analyses at all time points). Treatment failure rates were not different among groups (P = 0.75), and at 1 year after SLT, the percentage of patients maintaining a 20% IOP reduction ranged from 18% to 22% in the 3 study groups. CONCLUSIONS Anti-inflammatory therapy after SLT does not seem to substantially influence the IOP-lowering effect of SLT. In this study of patients with low baseline IOP, SLT showed limited efficacy in achieving a sustained reduction in IOP.