Optimal screening schedules for disease progression with application to diabetic retinopathy.
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ABSTRACT:
SUBMITTER: Bebu I
PROVIDER: S-EPMC6075595 | biostudies-literature | 2018 Jan
REPOSITORIES: biostudies-literature
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Optimal screening schedules for disease progression with application to diabetic retinopathy.
Biostatistics (Oxford, England) 20180101 1
Clinical management of chronic diseases requires periodic evaluations. Subjects transition between various levels of severity of a disease over time, one of which may trigger an intervention that requires treatment. For example, in diabetic retinopathy, patients with type 1 diabetes are evaluated yearly for either the onset of proliferative diabetic retinopathy (PDR) or clinically significant macular edema (CSME) that would require immediate treatment to preserve vision. Herein, we investigate m ...[more]
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Project description:The optimal schedules for breast cancer screening in terms of examination frequency and ages at examination are of practical interest. A decision-theoretic approach is explored to search for optimal cancer screening programs which should achieve maximum survival benefit while balancing the associated cost to the health care system. We propose a class of utility functions that account for costs associated with screening examinations and value of survival benefit under a non-stable disease model. We consider two different optimization criteria: optimize the number of screening examinations with equal screening intervals between exams but without a pre-fixed total cost; and optimize the ages at which screening should be given for a fixed total cost. We show that an optimal solution exists under each of the two frameworks. The proposed methods may consider women at different levels of risk for breast cancer so that the optimal screening strategies will be tailored according to a woman's risk of developing the disease. Results of a numerical study are presented and the proposed models are illustrated with various data inputs. We also use the data inputs from the Health Insurance Plan of New York (HIP) and Canadian National Breast Screening Study (CNBSS) to illustrate the proposed models and to compare the utility values between the optimal schedules and the actual schedules in the HIP and CNBSS trials. Here, the utility is defined as the difference in cure rates between cases found at screening examinations and cases found between screening examinations while accounting for the cost of examinations, under a given screening schedule.
| S-EPMC3230228 | biostudies-literature
Project description: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.
| S-EPMC6797087 | biostudies-literature
Project description:Aims/hypothesisThe aim of our study was to identify subgroups of patients attending the Scottish Diabetic Retinopathy Screening (DRS) programme who might safely move from annual to two yearly retinopathy screening.MethodsThis was a retrospective cohort study of screening data from the DRS programme collected between 2005 and 2011 for people aged ≥12 years with type 1 or type 2 diabetes in Scotland. We used hidden Markov models to calculate the probabilities of transitions to referable diabetic retinopathy (referable background or proliferative retinopathy) or referable maculopathy.ResultsThe study included 155,114 individuals with no referable diabetic retinopathy or maculopathy at their first DRS examination and with one or more further DRS examinations. There were 11,275 incident cases of referable diabetic eye disease (9,204 referable maculopathy, 2,071 referable background or proliferative retinopathy). The observed transitions to referable background or proliferative retinopathy were lower for people with no visible retinopathy vs mild background retinopathy at their prior examination (respectively, 1.2% vs 8.1% for type 1 diabetes and 0.6% vs 5.1% for type 2 diabetes). The lowest probability for transitioning to referable background or proliferative retinopathy was among people with two consecutive screens showing no visible retinopathy, where the probability was <0.3% for type 1 and <0.2% for type 2 diabetes at 2 years.Conclusions/interpretationTransition rates to referable diabetic eye disease were lowest among people with type 2 diabetes and two consecutive screens showing no visible retinopathy. If such people had been offered two yearly screening the DRS service would have needed to screen 40% fewer people in 2009.
| S-EPMC3699707 | biostudies-literature
Project description:PURPOSE: To assess the value of diabetic retinopathy (DR) severity as a possible predictive prognostic factor for the progression of chronic kidney disease (CKD). PATIENTS AND METHODS: Retrospective cohort study. Patients (51) who were initially diagnosed with DR and CKD were enrolled and their medical records were evaluated. The following ophthalmic factors were assessed by fluorescein angiography at the initial visit: area of capillary nonperfusion, presence of neovascularization and vitreous hemorrhage, and DR grade. The effect of these factors on CKD progression over the 2-year period of the study, defined as doubling of serum creatinine or the development of end-stage renal disease requiring dialysis or renal transplant, was evaluated. RESULTS: The study included 51 patients with DR and CKD; of these, 11 patients (21.6%) were found to have proliferative DR (PDR) and seven patients (13.7%) had high-risk PDR at baseline. Patients with ischemic DR, who showed extensive capillary nonperfusion (? 10 optic disc areas) in the retina, had a greater risk for CKD progression (hazard ratio = 6.64; P = 0.002). CONCLUSION: We found that extensive capillary nonperfusion in the retina greatly increased the risk of progression of CKD in patients with DR. This suggests that the retina and the kidney may have shared risk factors for microvascular disease secondary to diabetes mellitus, and emphasizes the need for a team approach to diabetes care.
| S-EPMC4166629 | biostudies-literature
Project description:AimsDiabetic retinopathy screening aims to detect people at risk of visual loss due to proliferative diabetic retinopathy, but also refers cases of suspected macular oedema (maculopathy). At the introduction of screening, ophthalmology was concerned that referral rates would be unmanageable. We report yield of referable disease by referral reason for the first 5?years of the programme.MethodsWe extracted screening results from a nationwide clinical diabetes database to calculate annual referral rates to ophthalmic clinics. We used logistic regression to examine associations between clinical measures and referable disease.Results182?397 people underwent ? 1successful retinal screening between 2006 and 2010. The yield of referable eye disease was highest in the first 2?years of screening (7.0% and 6.0%) before stabilising at ?4.3%. The majority of referrals are due to maculopathy with 73% of referrals in 2010 based on a finding of maculopathy.ConclusionsThe commonest cause for referral is for suspected macular oedema (maculopathy). Referral rates for retinopathy have stabilised, as predicted, at relatively low rates. However, ophthalmology workload continues to rise as new treatment options (ie, monthly intraocular injections) have unexpectedly increased the impact on ophthalmology. A review of the screening referral path for maculopathy may be timely.
| S-EPMC4033179 | biostudies-literature
Project description:Background/aimsTo determine if anaemia and oxygen delivery-related co-morbidities (ODCs) affect progression from non-proliferative diabetic retinopathy (NPDR) to vision-threatening diabetic retinopathy (VTDR).MethodsThis is a retrospective cohort study using medical claims data from a large US insurer. Cohorts were created from all NPDR patients between 2002 and 2016. Primary exclusion criteria consisted of any previous diagnosis of proliferative diabetic retinopathy (PDR), diabetic macular oedema (DME) or treatment used in the care of VTDR. The main outcome was a new diagnosis of VTDR (DME or PDR), PDR, or DME. A time-dependent, multivariate Cox proportional hazard regression was used to determine the association between anaemia and other ODCs with NPDR progression.ResultsOf the total 69,982 NPDR patients included for analysis, 12,270, 2,162, and 10,322 progressed to VTDR, PDR and DME, respectively. Both mild and moderate/severe (mod/sev) anaemia were associated with an increased hazard for progression to VTDR (mild HR:1.10, 95% CI:1.04-1.16, p < 0.001; mod/sev HR:1.20, 95% CI:1.12-1.29, p < 0.001), PDR (mild HR:1.29, 95% CI:1.13-1.46, p < 0.001; mod/sev HR:1.43, 95% CI:1.21-1.69, p < 0.001), and DME (mild HR:1.06, 95% CI:1.00-1.13, p < 0.001; mod/sev HR:1.14, 95% CI:1.05-1.24, p < 0.001). ODCs such as chronic pulmonary disease and history of blood disorder/cancer were also significantly associated with an increased hazard for NPDR progression (HR > 1.00, p < 0.001 for all comparisons).ConclusionsAnaemia, independent of kidney disease, appears to play a significant role in progression from NPDR to VTDR, PDR, or DME. Concurrently, association of ODCs with NPDR progression lends support to the underlying mechanisms of anaemia in the pathogenesis of diabetic retinopathy.
| S-EPMC7182576 | biostudies-literature
Project description: Not available
| S-EPMC6491139 | biostudies-literature
Project description:To determine the time and risk factors for developing proliferative diabetic retinopathy (PDR) and vitreous hemorrhage (VH).Multicenter, national cohort study.Anonymized data of 50 254 patient eyes with diabetes mellitus at 19 UK hospital eye services were extracted at the initial and follow-up visits between 2007 and 2014. Time to progression of PDR and VH were calculated with Cox regression after stratifying by baseline diabetic retinopathy (DR) severity and adjusting for age, sex, race, and starting visual acuity.Progression to PDR in 5 years differed by baseline DR: no DR (2.2%), mild (13.0%), moderate (27.2%), severe nonproliferative diabetic retinopathy (NPDR) (45.5%). Similarly, 5-year progression to VH varied by baseline DR: no DR (1.1%), mild (2.9%), moderate (7.3%), severe NPDR (9.8%). Compared with no DR, the patient eyes that presented with mild, moderate, and severe NPDR were 6.71, 14.80, and 28.19 times more likely to develop PDR, respectively. In comparison to no DR, the eyes with mild, moderate, and severe NPDR were 2.56, 5.60, and 7.29 times more likely to develop VH, respectively. In severe NPDR, the eyes with intraretinal microvascular abnormalities (IRMA) had a significantly increased hazard ratio (HR) of developing PDR (HR 1.77, 95% confidence interval [CI] 1.25-2.49, P = .0013) compared with those with venous beading, whereas those with 4-quadrant dot-blot hemorrhages (4Q DBH) had 3.84 higher HR of developing VH (95% CI 1.39-10.62, P = .0095).Baseline severities and features of initial DR are prognostic for PDR development. IRMA increases risk of PDR whereas 4Q DBH increases risk of VH.
| S-EPMC5608549 | biostudies-literature
Project description:AIM:To analyse retinopathy phenotypes and microaneurysm (MA) turnover in mild non-proliferative diabetic retinopathy (NPDR) as predictors of progression to diabetic central-involved macular oedema (CIMO) in patients with type 2 diabetes mellitus (DM) in two different ethnic populations. METHODS:205 patients with type 2 DM and mild NPDR were followed in a prospective observational study for 2 years or until development of CIMO, in two centres from different regions of the world. Ophthalmological examinations, including best-corrected visual acuity (BCVA), fundus photography with RetmarkerDR analysis, and optical coherence tomography (OCT), were performed at baseline and 6 12 and 24 months. RESULTS:158 eyes/patients reached either the study endpoint, CIMO (24) or performed the last study visit (24-month visit) without developing CIMO (134). From the eyes/patients in analysis, 27 eyes (17.1%) progressed to more advanced ETDRS (Early Treatment Diabetic Retinopathy Study) levels: 6 progressed to mild NPDR (level 35), 15 progressed to moderate NPDR (level 43), 5 progressed to moderately severe NPDR (level 47) and 1 progressed to high risk PDR (level 71). Worsening in ETDRS level is associated with phenotype C (p=0.005). From the 130 eyes/patients with a low MA turnover, 18 (13.8%) eyes/patients had an increase in ETDRS level, and from the 19 eyes/patients with a high MA turnover, 9 (47.4%) had an increase in ETDRS level (p<0.001). CONCLUSION:Eyes in the initial stages of diabetic retinopathy show different phenotypes with different risks for progression to CIMO. In phenotype C, MA turnover correlates with ETDRS grading worsening and development of CIMO.
| S-EPMC6362804 | biostudies-literature
Project description:BACKGROUND:Diabetic retinopathy (DR) is the leading cause of blindness among working-age adults worldwide. Early detection and treatment are necessary to forestall vision loss from DR. METHODS:A working group of ophthalmic and diabetes experts was established to develop a consensus on the key principles of an effective DR screening program. Recommendations are based on analysis of a structured literature review. RESULTS:The recommendations for implementing an effective DR screening program are: (1) Examination methods must be suitable for the screening region, and DR classification/grading systems must be systematic and uniformly applied. Two-field retinal imaging is sufficient for DR screening and is preferable to seven-field imaging, and referable DR should be well defined and reliably identifiable by qualified screening staff; (2) in many countries/regions, screening can and should take place outside the ophthalmology clinic; (3) screening staff should be accredited and show evidence of ongoing training; (4) screening programs should adhere to relevant national quality assurance standards; (5) studies that use uniform definitions of risk to determine optimum risk-based screening intervals are required; (6) technology infrastructure should be in place to ensure that high-quality images can be stored securely to protect patient information; (7) although screening for diabetic macular edema (DME) in conjunction with DR evaluations may have merit, there is currently insufficient evidence to support implementation of programs solely for DME screening. CONCLUSION:Use of these recommendations may yield more effective DR screening programs that reduce the risk of vision loss worldwide.
| S-EPMC7311555 | biostudies-literature