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Background: Findings from cardiovascular outcome trials suggest that treatment with fenofibrate may reduce the progression of diabetic retinopathy. However, no dedicated large‐scale randomised trials have yet investigated this hypothesis. Methods: LENS is a streamlined randomised double‐masked placebo‐controlled trial, based in Scotland, assessing whether treatment with fenofibrate (145 mg tablet daily or, in the context of impaired renal function, on alternate days) in people with early retinopathy reduces progression to referable diabetic retinopathy (defined in NHS Scotland's Diabetic Eye Screening grading scheme as referable background or proliferative retinopathy, or referable maculopathy in either eye) or treatment with retinal laser, intravitreal injections or vitrectomy. Adults with diabetes mellitus and non‐referable retinopathy (mild background retinopathy in both eyes or observable background retinopathy in one/both eyes at the most recent NHS retinal screening assessment; or observable maculopathy in one/both eyes in the previous 3 years) were eligible. Potential participants were identified from routinely collected healthcare data and followed up using regular contact from the research team and linkage to national electronic morbidity, mortality, biochemistry and retinal screening records. Study treatment was mailed to participants. Results: Between 18 September 2018 and 27 July 2021, 1151 participants were randomised. Their mean age was 61 (SD 12) years, 312 (27%) were female and 305 (26%) had type 1 diabetes. 96% had bilateral mild background retinopathy and 10% had observable maculopathy. Conclusions: LENS will provide a robust evaluation of the efficacy of treating people at risk of progression of diabetic retinopathy with fenofibrate. Results are anticipated in mid‐2024. Trial Registrations: NCT03439345; ISRCTN15073006; EuDRACT 2016–002656‐24. [ABSTRACT FROM AUTHOR]

Background: Findings from cardiovascular outcome trials suggest that fenofibrate therapy may reduce the progression of diabetic retinopathy. Methods: We recruited and followed adults with nonreferable diabetic retinopathy or maculopathy using the national Diabetic Eye Screening (DES) program in Scotland. We randomly assigned participants to receive 145-mg fenofibrate tablets or placebo (taken daily or, in those with impaired renal function, on alternate days). The primary outcome was a composite of developing referable diabetic retinopathy or maculopathy (based on Scotland's DES grading scheme) or treatment (intravitreal injection, retinal laser, vitrectomy) for retinopathy or maculopathy. Results: A total of 1151 participants were randomly assigned to treatment. During a median of 4.0 years, progression to referable diabetic retinopathy or maculopathy, or treatment thereof, occurred in 131 (22.7%) of 576 participants in the fenofibrate group and 168 (29.2%) of 575 in the placebo group (hazard ratio, 0.73; 95% confidence interval [CI], 0.58 to 0.91; P=0.006). In the fenofibrate group compared with the placebo group, the frequencies for any progression of retinopathy or maculopathy were 185 (32.1%) vs. 231 (40.2%); hazard ratio, 0.74; 95% CI, 0.61 to 0.90 and for the development of macular edema were 22 (3.8%) vs. 43 (7.5%); hazard ratio, 0.50; 95% CI, 0.30 to 0.84. Seventeen (3.0%) participants assigned fenofibrate and 28 (4.9%) assigned placebo were given treatment for retinopathy (hazard ratio, 0.58; 95% CI, 0.31 to 1.06). There was no effect on visual function, quality of life, or visual acuity. Trial-averaged estimated glomerular filtration rate was 7.9 (95% CI, 6.8 to 9.1) ml/min/1.73 m² lower in participants in the fenofibrate group compared with the placebo group. Serious adverse events occurred in 208 (36.1%) participants allocated fenofibrate and 204 (35.5%) participants allocated placebo. Conclusions: Fenofibrate reduced progression of diabetic retinopathy compared with placebo among participants with early retinal changes. (Funded by the National Institute for Health and Care Research; ClinicalTrials.gov number, NCT03439345; ISRCTN number, ISRCTN15073006.) [ABSTRACT FROM AUTHOR]

Context: Primary hyperparathyroidism (PHPT) is associated with increased risk of morbidity and death, and vitamin D levels are a potentially confounding variable. Objective: The aim of this study was to assess morbidity and mortality associated with primary hyperparathyroidism (PHPT). Methods: In this population-based retrospective matched cohort study, data linkage of biochemistry, hospital admissions, prescribing, imaging, pathology, and deaths was used to identify patients across the region of Tayside, Scotland, who had PHPT from 1997 to 2019. Cox proportional hazards models and hazards ratios (HR) were used to explore the relationship between exposure to PHPT and several clinical outcomes. Comparisons were made with an age- and gender-matched cohort. Results: In 11 616 people with PHPT (66.8% female), with a mean follow-up period of 8.8 years, there was an adjusted HR of death of 2.05 (95% CI, 1.97-2.13) for those exposed to PHPT. There was also an increased risk of cardiovascular disease (HR = 1.34; 95% CI, 1.24-1.45), cerebrovascular disease (HR = 1.29; 95% CI, 1.15-1.45), diabetes (HR = 1.39; 95% CI, 1.26-1.54), renal stones (HR = 3.02; 95% CI, 2.19-4.17) and osteoporosis (HR = 1.31; 95% CI, 1.16-1.49). Following adjustment for serum vitamin D concentrations (n = 2748), increased risks for death, diabetes, renal stones, and osteoporosis persisted, but not for cardiovascular or cerebrovascular disease. Conclusion: In a large population-based study, PHPT was associated with death, diabetes, renal stones, and osteoporosis, independent of serum vitamin D concentration. [ABSTRACT FROM AUTHOR]

Background National guidelines in most countries set screening intervals for diabetic retinopathy (DR) that are insufficiently informed by contemporary incidence rates. This has unspecified implications for interval disease risks (IDs) of referable DR, disparities in ID between groups or individuals, time spent in referable state before screening (sojourn time), and workload. We explored the effect of various screening schedules on these outcomes and developed an open-access interactive policy tool informed by contemporary DR incidence rates. Methods and findings Scottish Diabetic Retinopathy Screening Programme data from 1 January 2007 to 31 December 2016 were linked to diabetes registry data. This yielded 128,606 screening examinations in people with type 1 diabetes (T1D) and 1,384,360 examinations in people with type 2 diabetes (T2D). Among those with T1D, 47% of those without and 44% of those with referable DR were female, mean diabetes duration was 21 and 23 years, respectively, and mean age was 26 and 24 years, respectively. Among those with T2D, 44% of those without and 42% of those with referable DR were female, mean diabetes duration was 9 and 14 years, respectively, and mean age was 58 and 52 years, respectively. Individual probability of developing referable DR was estimated using a generalised linear model and was used to calculate the intervals needed to achieve various IDs across prior grade strata, or at the individual level, and the resultant workload and sojourn time. The current policy in Scotland-screening people with no or mild disease annually and moderate disease every 6 months-yielded large differences in ID by prior grade (13.2%, 3.6%, and 0.6% annually for moderate, mild, and no prior DR strata, respectively, in T1D) and diabetes type (2.4% in T1D and 0.6% in T2D overall). Maintaining these overall risks but equalising risk across prior grade strata would require extremely short intervals in those with moderate DR (1-2 months) and very long intervals in those with no prior DR (35-47 months), with little change in workload or average sojourn time. Changing to intervals of 12, 9, and 3 months in T1D and to 24, 9, and 3 months in T2D for no, mild, and moderate DR strata, respectively, would substantially reduce disparity in ID across strata and between diabetes types whilst reducing workload by 26% and increasing sojourn time by 2.3 months. Including clinical risk factor data gave a small but significant increment in prediction of referable DR beyond grade (increase in C-statistic of 0.013 in T1D and 0.016 in T2D, both p < 0.001). However, using this model to derive personalised intervals did not have substantial workload or sojourn time benefits over stratum-specific intervals. The main limitation is that the results are pertinent only to countries that share broadly similar rates of retinal disease and risk factor distributions to Scotland. Conclusions Changing current policies could reduce disparities in ID and achieve substantial reductions in workload within the range of IDs likely to be deemed acceptable. Our tool should facilitate more rational policy setting for screening., Author(s): Andreas Ochs 1, Stuart McGurnaghan 1, Mike W. Black 2, Graham P. Leese 3, Sam Philip 4, Naveed Sattar 5, Caroline Styles 6, Sarah H. Wild 7, Paul M. [...]

ABSTRACT The two-compound ointment (Taclonex[R]/Daivobet[R]/Dovobet[R] ointment) combining calcipotriene 50 [micro]g/g and betamethasone 0.5 mg/g (as dipropionate) is very effective in the treatment of psoriasis vulgaris. There is a possibility that [...]