No relationship between socioeconomic status, education level and development and progression of diabetic retinopathy in type 2 diabetes: a FIELD trial substudy.

In 6002 Australian adults with type 2 diabetes and a median 5-year follow-up in the FIELD (Fenofibrate Intervention and Event Lowering in Diabetes) trial, baseline socioeconomic status (SES) and self-reported education level were not related to development of on-trial sight-threatening diabetic retinopathy. Similarly, in a retinal photography substudy (n = 549), two-step diabetic retinopathy progression was not related to SES or education.

Review and comparison of retinal vessel calibre and geometry software and their application to diabetes, cardiovascular disease, and dementia.

Developments in retinal imaging technologies have enabled the quantitative evaluation of the retinal vasculature. Changes in retinal calibre and/or geometry have been reported in systemic vascular diseases, including diabetes mellitus (DM), cardiovascular disease (CVD), and more recently in neurodegenerative diseases, such as dementia. Several retinal vessel analysis softwares exist, some being disease-specific, others for a broader context. In the research setting, retinal vasculature analysis using semi-automated software has identified associations between retinal vessel calibre and geometry and the presence of or risk of DM and its chronic complications, and of CVD and dementia, including in the general population. In this article, we review and compare the most widely used semi-automated retinal vessel analysis softwares and their associations with ocular imaging findings in common systemic diseases, including DM and its chronic complications, CVD, and dementia. We also provide original data comparing retinal calibre grading in people with Type 1 DM using two softwares, with good concordance.

Adherence to the Mediterranean Diet and Successful aging in Greeks living in Greece and abroad: the epidemiological Mediterranean Islands Study (MEDIS).

Background: Whether older immigrant populations from the Mediterranean region, continue to follow the MD long after they immigrated is not known. Aim: Compare adherence to the MD and successful aging levels between Greeks living in Greece (GG) and Greeks living abroad (GA). Methods: Anthropometrical, clinical, psychological, sociodemographic, dietary and lifestyle parameters were assessed in a cross-sectional manner in a sample of 252 GG and 252 GA. Mediterranean Diet Score (MedDietScore range 0-55) was used to assess adherence to the MD. Successful aging was evaluated with the validated successful aging index (SAI range 0-10). Results: GA presented higher adherence to MD (p < 0.001); they were consuming significantly more cereals, legumes, vegetables, and fruits compared to GG. GG consumed significantly more dairy (3.8 ± 2.9 vs. 1.9 ± 2.2, p < 0.001) and potatoes (2.4 ± 1.6 vs. 1.9 ± 1.5, p < 0.001) compared to GA. Meat (p = 0.27), poultry (p = 0.72), fish (p = 0.68), olive oil (p = 0.16) and alcohol consumption (p = 0.05) were comparable between the two groups (all p's > 0.05). MedDietScore was positively associated with SAI among both groups after adjusting for possible confounders (0.041 ± 0.014, p = 0.003 GG and 0.153 ± 0.035, p < 0.001 GA). Also, legumes, cereals, fruits and vegetables were found to be beneficial for successful aging. Conclusion: Adherence to the MD is associated with higher levels of successful aging among people of the same genetic background living in different environments. However, traditional dietary habits are gradually abandoned in their native countries, when, at the same time, are considered cultural heritage and preserved accordingly among immigrants.

Prevalence of diabetic retinopathy and reduced vision among indigenous Australians in the nurse-led integrated Diabetes Education and Eye Screening study in a regional primary care clinic.

BACKGROUND: Nationally, Indigenous Australians are more likely to have diabetes and diabetic retinopathy (DR) than non-Indigenous Australians. However, the prevalence of DR and impaired vision in regional primary care settings is unclear. AIM: To describe the prevalence and severity of DR and presenting vision level among Indigenous Australian adults with diabetes attending an indigenous primary care clinic in regional Australia. METHODS: Participants underwent nurse-led retinal imaging and DR screening with offsite retinal grading in the integrated Diabetes Education and Eye Screening (iDEES) project implemented at a regional indigenous primary healthcare setting between January 2018 and March 2020. RESULTS: Of 172 eligible adults, 135 (79%) were recruited and screened for DR and vision level. The median age was 56 (46-67) years, 130 (96%) had type 2 diabetes of median (interquartile range) duration 6 (2-12) years and 48 (36%) were male. Images from 132 (97.8%) participants were gradable. DR was present in 38 (29%) participants: mild non-proliferative in 33 (25%); moderate-severe in three (2.5%); and sight-threatening two (1.5%). Subnormal presenting vision was present in 33%. CONCLUSIONS: A nurse-led model of care integrating diabetes eye screening and education at a single visit was successful at recruiting Indigenous Australian adults with diabetes, screening their vision and acquiring a high rate of gradable images. Even for a short duration of known diabetes, DR was present in three out of 10 patients screened.

Nurse-led vascular risk assessment in a regional Victorian Indigenous primary care diabetes clinic: An integrated Diabetes Education and Eye disease Screening [iDEES] study.

AIM: The aim was to describe vascular risk factors in Australian adults with diabetes attending an Indigenous primary care nurse-led diabetes clinic. DESIGN: This was a cross-sectional descriptive single-site study. METHODS: Vascular risk factor data were extracted from the electronic health records of participants in the nurse-led integrated Diabetes Education and Eye disease Screening (iDEES) study at a regional Victorian Indigenous primary health-care clinic between January 2018 and March 2020. RESULTS: Of 172 eligible adults, 135 (79%) provided data. Median (IQR) age was 56 (46-67) years; 89% were Indigenous; 95% had Type 2 diabetes of median (IQR) duration of 6 (2-12) years and 48 (36%) were male. Median HbA1c, blood pressure, cholesterol (total; LDL and HDL), triglycerides, eGFR, CRP and BMI were 8.0% (64 mmol/mol), 127/78 mm Hg, 4.2; 1.9; 1.1 mmol/L, 2.3 mmol/L, 89 ml/min/1.73 m2 , 7.0 mg/L and 32.4 kg/m2 . Of nine clinical risk factors, the median (IQR) number of risk factors at target was 4 (3-5) for women and 3 (2-5) for men, pχ2  = 0.563. Clinical targets for BMI, HbA1c, blood pressure, triglycerides, total cholesterol, LDL cholesterol, urine albumin: creatinine ratio, HDL cholesterol and smoking were met by 14%, 34%, 38%, 39%, 44%, 52%, 54%, 62% and 64%, respectively. CONCLUSION: A nurse-led model of integrated clinical risk factor assessment and diabetes education identified suboptimal levels of clinical risk factor control for avoiding diabetes chronic complications amongst Australian adults with diabetes in an Indigenous primary care setting. IMPACT: A nurse-led model of diabetes care integrating clinical risk factor assessment into a diabetes education service is achievable. Understanding by stakeholders, including people with diabetes, their clinicians and health services, of the importance of regular monitoring of risk factors impacting diabetes complications is important. The novel nurse-managed iDEES primary-care model of care can assist. TRIAL REGISTRATION: This study was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12618001204235).

Fenofibrate, which reduces risk of sight-threatening diabetic retinopathy in type 2 diabetes, is associated with early narrowing of retinal venules: a FIELD trial substudy.

Retinal vessel calibre metrics were evaluated at baseline and 2 years in a FIELD substudy (n = 208). Central retinal venule calibre was significantly reduced by fenofibrate and unchanged by placebo. Arteriole metrics did not change. Larger studies relating retinal vessel calibre to future diabetes complications and response to therapy are merited.

Retinopathy risk calculators in the prediction of sight-threatening diabetic retinopathy in type 2 diabetes: A FIELD substudy.

AIMS: To evaluate the risk algorithm by Aspelund et al. for predicting sight-threatening diabetic retinopathy (STDR) in Type 2 diabetes (T2D), and to develop a new STDR prediction model. METHODS: The Aspelund et al. algorithm was used to calculate STDR risk from baseline variables in 1012 participants in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) ophthalmological substudy, compared to on-trial STDR status, and receiver operating characteristic analysis performed. Using multivariable logistic regression, traditional risk factors and fenofibrate allocation as STDR predictors were evaluated, with bootstrap-based optimism-adjusted estimates of predictive performance calculated. RESULTS: STDR developed in 28 participants. The Aspelund et al. algorithm predicted STDR at 2- and 5-years with area under the curve (AUC) 0.86 (95% CI 0.77-0.94) and 0.86 (0.81-0.92), respectively. In the second model STDR risk factors were any DR at baseline (OR 24.0 [95% CI 5.53-104]), HbA1c (OR 1.95 [1.43-2.64]) and male sex (OR 4.34 [1.32-14.3]), while fenofibrate (OR 0.13 [0.05-0.38]) was protective. This model had excellent discriminatory ability (AUC = 0.89). CONCLUSIONS: The algorithm by Aspelund et al. predicts STDR well in the FIELD ophthalmology substudy. Logistic regression analysis found DR at baseline, male sex, and HbA1c were predictive of STDR and, fenofibrate was protective.

Mixed diabetic retinopathy screening coverage results in Indigenous Australian primary care settings: A nurse-led model of integrated diabetes care.

AIMS: To determine eye screening coverage and adherence to national eye screening recommendations of a nurse-led retinal image-based model of diabetes education and eye screening in Indigenous primary care clinics. DESIGN: A pre-post study. METHODS: During January 2018-March 2020 Indigenous Australians with diabetes at three regional Australian clinics were offered eye screening by a nurse-diabetes educator/retinal imager. At the main site the nurse recruited/scheduled participants, and at satellite sites local clinic staff did so. Visual acuity was tested and digital retinal images acquired and graded. Participants were offered rescreening at or before 12-months based on baseline results. RESULTS: In total 203 adults with diabetes attending Indigenous primary care clinics were screened, with divergent results based on the recruitment methods. At the main clinic 135 of 172 eligible adults (79%) were screened. At the satellite sites, 15 of 85 (18%) and 21 of 77 (27%) diabetes patients were screened. Combined coverage 51%. CONCLUSION: A credentialed nurse-educator implemented a model of retinal image-based diabetes education, measured eye screening coverage and adherence to national eye screening guidelines, met the 'acceptable 75% eye screening coverage' benchmark and improved patient eye screening guideline adherence at the one site where the nurse-educator had access to patient recruitment and scheduling. IMPACT: This novel nurse-led primary care iDEES model of retinal image-based diabetes education can improve the currently low Indigenous diabetes eye screening coverage in Australia. Importantly, the nurse-managed iDEES model of integrated diabetes care is readily adaptable to other settings and populations where access to and/or uptake of eye care is suboptimal. CLINICAL TRIAL REGISTRATION: ANZCTRN1261800120435.

Health-risk behaviours among Indigenous Australians with diabetes: A study in the integrated Diabetes Education and Eye Screening (iDEES) project.

AIM: To assess the prevalence of modifiable health-risk behaviours among Indigenous Australian adults with diabetes attending a regional Victorian Indigenous primary-care clinic. DESIGN: A cross-sectional observational single-site study. METHODS: As part of a multi-study project we administered the Smoking, Nutrition, Alcohol consumption, Physical activity and Emotional wellbeing (SNAPE) survey tool during the study baseline visit to methodically capture health-related behavioural data in the nurse-led integrated Diabetes Education and Eye Screening (iDEES) project in a regional Indigenous primary healthcare setting between January 2018 and March 2020. This descriptive SNAPE study helps address the lack of health behaviour data for Indigenous people with diabetes. RESULTS: Of 172 eligible adults, 135 (79%) were recruited to the iDEES study, 50 (37%) male. All participated in at least one survey. Median (range) age was 56 (46-67) years; 130 (96%) had Type 2 diabetes of median [IQR] duration 6 (2-12) years. All 135 provided smoking data; 88 (65%) completed all surveys. Forty-nine (36%) and 29 (22%) were current or former smokers, respectively; 5 (6%) met vegetable intake guidelines, 22 (25%) met fruit intake guidelines; 38 [43%] drank alcohol in the past year. On average, participants walked for ≥10 min at a time 4 days/week and sat for an average of 8 h on weekdays; 35 (40%) had minimal-mild, and 30 (34%) had moderate-severe depressive symptoms. CONCLUSION: Suboptimal modifiable health-risk behaviours and depressive symptoms are common in Indigenous Australian adults with diabetes. IMPACT: Orderly assessment and reporting of health-risk behaviours using a single multi-component survey instrument (SNAPE tool) during a nurse-led diabetes education clinical visit is feasible and efficient. Such data may facilitate personalised interventions and improve diabetes management at both individual and health service levels.

Successful aging and lifestyle comparison of Greeks living in Greece and abroad: the epidemiological Mediterranean Islands Study (MEDIS).

OBJECTIVES: Comparing lifestyle and successful aging between Greeks living in Greece (GG) and Greeks living abroad (GA) using a multidimensional model of successful aging including both biomedical and non-medical components. METHODS: Anthropometric, clinical, psychological, socio-demographic, dietary and lifestyle parameters were assessed in a random sample of 252 GG and 252 GA. Successful aging was evaluated using the validated successful aging index (SAI range 0-10). RESULTS: GA had better financial and educational status and scored higher in all social activity parameters (p's < 0.05). GA were more likely to be physically active (p < 0.001), had higher adherence to the Mediterranean diet (p < 0.001) and were less likely to be smoking (p = 0.008). Depression was more evident among GG compared to GA (p < 0.001). GA was aging significantly more successfully than GG (p < 0.001). Men irrespective of location were aging significantly more successfully than women (p < 0.05). CONCLUSION: Place of residence and personal choices significantly affect the level of healthy aging among people with similar genetic backgrounds.

Associations with sight-threatening diabetic macular oedema among Indigenous adults with type 2 diabetes attending an Indigenous primary care clinic in remote Australia: a Centre of Research Excellence in Diabetic Retinopathy and Telehealth Eye and Associated Medical Services Network study.

OBJECTIVE: To identify factors associated with sight-threatening diabetic macular oedema (STDM) in Indigenous Australians attending an Indigenous primary care clinic in remote Australia. METHODS AND ANALYSIS: A cross-sectional study design of retinopathy screening data and routinely-collected clinical data among 236 adult Indigenous participants with type 2 diabetes (35.6% men) set in one Indigenous primary care clinic in remote Australia. The primary outcome variable was STDM assessed from retinal images. RESULTS: Age (median (range)) was 48 (21-86) years, and known diabetes duration (median (range)) was 8.0 (0-24) years. Prevalence of STDM was high (14.8%) and similar in men and women. STDM was associated with longer diabetes duration (11.7 vs 7.9 years, respectively; p<0.001) and markers of renal impairment: abnormal estimated Glomerular Filtration Rate (eGFR) (62.9 vs 38.3%, respectively; p=0.007), severe macroalbuminuria (>300 mg/mmol) (20.6 vs 5.7%, respectively; p=0.014) and chronic kidney disease (25.7 vs 12.2%, respectively; p=0.035). Some clinical factors differed by sex: anaemia was more prevalent in women. A higher proportion of men were smokers, prescribed statins and had increased albuminuria. Men had higher blood pressure, but lower glycated Haemoglobin A1c (HbA1c) levels and body mass index, than women. CONCLUSION: STDM prevalence was high and similar in men and women. Markers of renal impairment and longer diabetes duration were associated with STDM in this Indigenous primary care population. Embedded teleretinal screening, known diabetes duration-based risk stratification and targeted interventions may lower the prevalence of STDM in remote Indigenous primary care services. TRIAL REGISTRATION NUMBER: Australia and New Zealand Clinical Trials Register: ACTRN 12616000370404.

Facilitating diabetic retinopathy screening using automated retinal image analysis in underresourced settings.

AIM: To evaluate an automated retinal image analysis (ARIA) of indigenous retinal fundus images against a human grading comparator for the classification of diabetic retinopathy (DR) status. METHODS: Indigenous Australian adults with type 2 diabetes (n = 410) from three remote and very remote primary-care services in the Northern Territory, Australia, underwent teleretinal DR screening. A single, central retinal fundus photograph (opportunistic mydriasis) for each eye was later regraded using a single ARIA and a UK human grader and national DR classification system. The sensitivity and specificity of ARIA were assessed relative to the comparator. Proportionate agreement and a Kappa statistic were also computed. RESULTS: Retinal images from 391 and 393 participants were gradable for 'Any DR' by the human grader and ARIA grader, respectively. 'Any DR' was detected by the human grader in 185 (47.3%) participants and by ARIA in 202 (48.6%) participants (agreement =88.0%, Kappa = 0.76,), whereas proliferative DR was detected in 31 (7.9%) and 37 (9.4%) participants (agreement = 98.2%, Kappa = 0.89,), respectively. The ARIA software had 91.4 (95% CI, 86.3-95.0) sensitivity and 85.0 (95% CI, 79.3-89.5) specificity for detecting 'Any DR' and 96.8 (95% CI, 83.3-99.9) sensitivity and 98.3 (95% CI, 96.4-99.4) specificity for detecting proliferative DR. CONCLUSIONS: This ARIA software has high sensitivity for detecting 'Any DR', hence could be used as a triage tool for human graders. High sensitivity was also found for detection of proliferative DR by ARIA. Future versions of this ARIA should include maculopathy and referable DR (CSME and/or PDR). Such ARIA software may benefit diabetes care in less-resourced regions.

A model of culturally-informed integrated diabetes education and eye screening in indigenous primary care services and specialist diabetes clinics: Study protocol.

AIMS: To improve diabetes management in Indigenous Australians using an integrated nurse-led model of diabetes education and eye screening in indigenous primary care and specialist diabetes clinics. DESIGN: A pre-post study. METHODS: This study will be implemented in indigenous primary care and specialist diabetes clinics in Victoria, Australia. Participants recruited to the study will be existing adult patient with diagnosed diabetes attending study sites. A nurse-credentialled diabetes educator and certified retinal imager will deliver three study components: (a) retinal photography as a diabetic retinopathy screening and patient engagement tool; (b) lifestyle and behaviour surveys, administered at baseline and at the final visit, in 12 months. Findings from the surveys and participants' retinal images will be used to guide; and (c) personalized diabetes education. The primary outcomes are participant adherence to diabetic eye screening recommendations and health service diabetic retinopathy screening coverage. Secondary outcomes are baseline DR prevalence and changes in clinical and lifestyle risk factor levels, diabetes knowledge and satisfaction with diabetes care. DISCUSSION: Compared with non-indigenous Australians, Indigenous Australians have a high prevalence of diabetic retinopathy and blindness, low adherence to eye screening recommendations and suboptimal health literacy. Nurse-credentialled diabetes educators can be trained to incorporate retinal imaging and eye screening into their clinical practice to give image-based diabetes education to facilitate diabetic retinopathy management. IMPACT: Credentialled nurse diabetes educators who integrate eye screening and diabetes education can facilitate timelier diabetic retinopathy screening, referral pathways and treatment of sight-threatening retinopathy. We believe that this model of integrated diabetes education and eye screening will also improve adherence to eye screening recommendations, population screening coverage, health literacy, risk factor levels and diabetes self-care. CLINICAL TRIAL REGISTRATION: ANZCTRN1261800120435.

Imaging the eye and its relevance to diabetes care.

Diabetes is a major cause of vision loss globally, yet this devastating complication is largely preventable. Early detection and treatment of diabetic retinopathy necessitates screening. Ocular imaging is widely used clinically, both for the screening and management of diabetic retinopathy. Common eye conditions, such as glaucoma, cataracts and retinal vessel thrombosis, and signs of systemic conditions, such as hypertension, are frequently revealed. As well as imaging by a skilled clinician during an eye examination, non-ophthalmic clinicians, such as general practitioners, endocrinologists, nurses and trained health workers, can also can carry out diabetic eye screening. This process usually comprises local imaging with remote grading, mostly human grading. However, grading incorporating artificial intelligence is emerging. In a clinical research context, retinal vasculature analyses using semi-automated software in many populations have identified associations between retinal vessel geometry, such as vessel caliber, and the risk of diabetic retinopathy and other chronic complications of type 1 and type 2 diabetes. Similarly, evaluation of corneal nerves by corneal confocal microscopy is revealing diabetes-related abnormalities, and associations with and predictive power for other chronic diabetes complications. As yet, the value of retinal vessel geometry and corneal confocal microscopy measures at an individual level is uncertain. In this article, targeting non-ocular clinicians and researchers, we review existent and emerging ocular imaging and grading tools, including artificial intelligence, and their associations between ocular imaging findings and diabetes and its chronic complications.

Screening for diabetic retinopathy and reduced vision among Indigenous Australians in Top End primary care health services: a TEAMSnet sub-study.

BACKGROUND: Diabetic retinopathy (DR) prevalence is higher in Indigenous Australians than in other Australians and is a major cause of vision loss. Consequently, timely screening and treatment is paramount, and annual eye screening is recommended for Indigenous Australians. AIMS: To assess the prevalence of DR, reduced vision and DR treatment coverage among Indigenous Australian adults with diabetes attending Top End indigenous primary care health services. METHODS: A cross-sectional DR screening study conducted from November 2013 to December 2015 in two very remote Northern Territory Aboriginal primary healthcare services. RESULTS: In 287 subjects, the prevalence of non-proliferative DR, proliferative DR and clinically significant diabetic macular oedema was 37.3%, 5.4% and 9.0% respectively. Treatment coverage for PDR was 60% (of 10 patients) and for CSMO was 17% (of 23 patients). Vision data were available from 122 participants at one site. The proportion with normal vision, reduced vision, impaired vision and blindness was 31.1%, 52.5%, 15.6% and 0.8% respectively. Overall, ungradable monocular image sets (46%) were associated with poorer quality images and missing protocol images (both P < 0.001). Ungradable images for DR were associated with presence of small pupils/media opacities (P < 0.001). Ungradable images for diabetic macular oedema were associated with poorer image quality (P < 0.001), cataracts (P < 0.001) and small pupils (P = 0.04). CONCLUSIONS: A high prevalence of DR, CSMO and impaired vision was noted in Indigenous Australians with diabetes. Screening in primary care is feasible, but more effective screening methods are needed.

Visual Outcomes in the Management of Diabetic Maculopathy in Central Australia.

PURPOSE: In major urban centres and high-resource settings, treatment of diabetic maculopathy with anti-Vascular Endothelial Growth Factor (VEGF) injections has largely displaced laser treatment. However, intravitreal therapy alone requires frequent follow-up, a barrier to adherence in remote Australia. We report vision outcomes of phased diabetic maculopathy treatment in remote Central Australia for maculopathy using laser and, in a subset, supplementary injection treatment. METHODS: We audited clinical records of patients undergoing laser treatment for diabetic maculopathy between 2001 and 2013 at an ophthalmology service based at Alice Springs Hospital, a regional hub in remote Australia. All patients receiving macular laser treatment were included, and some required supplementary injection(s). The primary outcome measure was change in best-corrected visual acuity [BCVA] from baseline treatment. RESULTS: Of 338 maculopathy-treated patients, 88% were indigenous and 39% were male. Of 554 maculopathy laser-treated eyes, 118 (21%) received supplementary injection/s. In the laser treatment phase, median BCVA was 78 letters at baseline (interquartile range 62-80) and decreased by a median of two letters at final visit. In the subset who underwent subsequentinjection treatment, BCVA was 60 letters at first injection, with a median five-letter increase by final visit. Overall outcomes were similar in Indigenous and non-Indigenous Australians. Predictors of reduction in BCVA in the macular laser treatment phase were better baseline BCVA, older age, and PRP treatment (all p < .005). CONCLUSION: Laser treatment for diabetic maculopathy preserved vision in Central Australia, where barriers to follow-up can preclude regular injections. Supplementary injections stabilized vision in the laser-resistant subset.

Integrating diabetic retinopathy screening within diabetes education services in Australia's diabetes and indigenous primary care clinics.

As diabetes occurs in all ethnicities and regions it is essential that retinopathy screening be widely available. Screening rates are lower in Indigenous than in non-Indigenous Australians. Technological advances and Medicare rebates should facilitate improved outcomes. Use of non-ophthalmic clinicians, (general practitioners, diabetes educators, health-workers and endocrinologists) to supplement coverage by ophthalmologists and optometrists would extend retinopathy screening capacity. Diabetes educators are an integral part of diabetes management. Integrating ocular screening and diabetes education in primary care settings has potential to improve synergistically retinopathy screening coverage, patient self-management, risk factor control, care satisfaction, health economics and sustainability of under-resourced services.

Correction to: A randomised controlled trial of dietary improvement for adults with major depression (the 'SMILES' trial).

The original version of this paper [1] did not specify that a website was used in the final year of recruitment, in addition to the other stated recruitment methods.

The SMILES trial: an important first step.

The SMILES trial was the first intervention study to test dietary improvement as a treatment strategy for depression. Molendijk et al. propose that expectation bias and difficulties with blinding might account for the large effect size. While we acknowledge the issue of expectation bias in lifestyle intervention trials and indeed discuss this as a key limitation in our paper, we observed a strong correlation between dietary change and change in depression scores, which we argue is consistent with a causal effect and we believe unlikely to be an artefact of inadequate blinding. Since its publication, our results have been largely replicated and our recent economic evaluation of SMILES suggests that the benefits of our approach extend beyond depression. We argue that the SMILES trial should be considered an important, albeit preliminary, first step in the field of nutritional psychiatry research.