Trends of chronic illness in emergency department admissions among elderly adults in a tertiary hospital over ten years.

BACKGROUND: This study aimed to determine to what extent an aging population and shift to chronic illness has contributed to emergency admissions at a tertiary care hospital over ten years. METHODS: This was a retrospective observational study performed using a database of all emergency admissions from the Emergency Department (ED) at a single tertiary hospital in Singapore during a ten-year period (January 1st, 2008 to December 31st, 2017). Emergency admissions were defined as ED visits with inpatient admission as the disposition. This study analyzed the trends of demographics, pre-existing comorbidities, chronic conditions or ambulatory care sensitive conditions (ACSC) of all patients who underwent emergency admissions in Singapore General Hospital. RESULTS: A total of 446,484 emergency records were included. For elderly patients, the proportions of them had pre-existing multimorbidity at the time of undergoing emergency admissions were found to be lower at the end the 10-year study period relative to the beginning of the study period. The proportions of emergency admissions whose ED primary diagnoses were categorized as chronic conditions and certain chronic ACSC including chronic obstructive pulmonary disease, congestive heart failure, diabetes complications, and epilepsy also decreased for elderly patients over the 10-year study period. CONCLUSIONS: In Singapore, despite a rapidly aging population, there have been surprisingly lower proportions of chronic conditions, pre-existing comorbidities, and chronic ACSC among the elderly emergency admissions. This is possibly consistent with an overall improved management of the chronic conditions among the elderly population. Future studies should include similar studies at the national level and comparison with other healthcare settings in different countries.

Safety and efficacy of plasmid DNA expressing two isoforms of hepatocyte growth factor in patients with critical limb ischemia.

VM202, a plasmid DNA that expresses two isoforms of hepatocyte growth factor, may elicit angiogenic effects that could benefit patients with critical limb ischemia (CLI). In a phase 2, double-blind trial in 52 CLI patients, we examined the safety and potential efficacy of intramuscular injections of low-dose (n=21) or high-dose (n=20) VM202 or placebo (n=11) in the affected limb (days 0, 14, 28 and 42). Adverse events and serious adverse events were similar among the groups; no malignancy or proliferative retinopathy was seen. In exploratory efficacy analyses, we found no differences in ankle or toe-brachial index, VAS, VascuQuol or amputation rate among the groups. Complete ulcer healing was significantly better in high-dose (8/13 ulcers; P<0.01) versus placebo (1/9) patients. Clinically meaningful reductions (>50%) in ulcer area occurred in high-dose (9/13 ulcers) and low-dose (19/27) groups versus placebo (1/9; P<0.05 and P<0.005, respectively). At 12 months, significant differences were seen in TcPO2 between the high-dose and placebo groups (47.5 ± 17.8 versus 36.6 ± 24.0 mm Hg, respectively; P<0.05) and in the change from baseline among the groups (P<0.05). These data suggest that VM202 is safe and may provide therapeutic bioactivity in CLI patients.

Improving docking results via reranking of ensembles of ligand poses in multiple X-ray protein conformations with MM-GBSA.

There is a tendency in the literature to be critical of scoring functions when docking programs perform poorly. The assumption is that existing scoring functions need to be enhanced or new ones developed in order to improve the performance of docking programs for tasks such as pose prediction and virtual screening. However, failures can result from either sampling or scoring (or a combination of the two), although less emphasis tends to be given to the former. In this work, we use the programs GOLD and Glide on a high-quality data set to explore whether failures in pose prediction and binding affinity estimation can be attributable more to sampling or scoring. We show that identification of the correct pose (docking power) can be improved by incorporating ligand strain into the scoring function or rescoring an ensemble of diverse docking poses with MM-GBSA in a postprocessing step. We explore the use of nondefault docking settings and find that enhancing ligand sampling also improves docking power, again suggesting that sampling is more limiting than scoring for the docking programs investigated in this work. In cross-docking calculations (docking a ligand to a noncognate receptor structure) we observe a significant reduction in the accuracy of pose ranking, as expected and has been reported by others; however, we demonstrate that these alternate poses may in fact be more complementary between the ligand and the rigid receptor conformation, emphasizing that treating the receptor rigidly is an artificial constraint on the docking problem. We simulate protein flexibility by the use of multiple crystallographic conformations of a protein and demonstrate that docking results can be improved with this level of protein sampling. This work indicates the need for better sampling in docking programs, especially for the receptor. This study also highlights the variable descriptive value of RMSD as the sole arbiter of pose replication quality. It is shown that ligand poses within 2 Å of the crystallographic one can show dramatic differences in calculated relative protein-ligand energies. MM-GBSA rescoring of distinct poses overcomes some of the sensitivities of pose ranking experienced by the docking scoring functions due to protein preparation and binding site definition.

Normative reference values, determinants and regression equations for the incremental shuttle walk test (ISWT) in healthy Asian population aged 21 to 80 years.

BACKGROUND: The validated Incremental Shuttle Walk Test (ISWT) is widely used for evaluating maximal exercise capacity, with the distance-walked (IWSD) as the primary outcome. However, there are no normative reference values (NRV) and reference equations to predict ISWD for the Singaporean population. OBJECTIVES: This study aims to establish the NRV and reference equations for ISWD in healthy Singaporeans aged 21 to 80 and investigate the determining variables during ISWT. METHODS: This cross-sectional study recruited community-dwelling healthy subjects aged 21-80 from the community via convenience sampling. Each subject completed two trials of the ISWT according to the standard protocol. Variables measured during the trials included ISWD, pre-and post-test heart rate (HR), oxygen saturation, blood pressure (BP), modified Borg's dyspnoea score and Borg's rate of perceived exertion (RPE). RESULTS: 199 healthy Singaporean (females = 114, males = 85) participated in the study. The overall median ISWD was 660.0 metres (m) [interquartile range (IQR):440.0-850.0]. The age-stratified mean ISWD ranged from 430.0 m (IQR:350.0-450.0) (aged 60-80) to 480.0 m (IQR:438.0-650.0) (aged 40-59) to 780.0 m (IQR:670.0-960.0) (aged 21-39). Gender, age, weight, height and HR change (highest post-test HR minus pre-test HR) were the most significant variables (p < 0.001). IWSD (m) = 651.4(Height, m) +89.7(Gender, male = 1; female = 0) -6.31(Age, years) -3.61(Weight, kilograms) +2.54(HR change, beats per minute); R2 = 0.741. Previously published ISWT reference equations cannot accurately predict the ISWD in the Singaporean population. CONCLUSIONS: This study investigated the ISWD NRV and established reference equations for healthy Singaporeans aged 21-80. The information would be beneficial in setting performance benchmarks to guide physical assessment, intervention and rehabilitation.

Ancient Lowland Maya neighborhoods: Average Nearest Neighbor analysis and kernel density models, environments, and urban scale.

Many humans live in large, complex political centers, composed of multi-scalar communities including neighborhoods and districts. Both today and in the past, neighborhoods form a fundamental part of cities and are defined by their spatial, architectural, and material elements. Neighborhoods existed in ancient centers of various scales, and multiple methods have been employed to identify ancient neighborhoods in archaeological contexts. However, the use of different methods for neighborhood identification within the same spatiotemporal setting results in challenges for comparisons within and between ancient societies. Here, we focus on using a single method-combining Average Nearest Neighbor (ANN) and Kernel Density (KD) analyses of household groups-to identify potential neighborhoods based on clusters of households at 23 ancient centers across the Maya Lowlands. While a one-size-fits all model does not work for neighborhood identification everywhere, the ANN/KD method provides quantifiable data on the clustering of ancient households, which can be linked to environmental zones and urban scale. We found that centers in river valleys exhibited greater household clustering compared to centers in upland and escarpment environments. Settlement patterns on flat plains were more dispersed, with little discrete spatial clustering of households. Furthermore, we categorized the ancient Maya centers into discrete urban scales, finding that larger centers had greater variation in household spacing compared to medium-sized and smaller centers. Many larger political centers possess heterogeneity in household clustering between their civic-ceremonial cores, immediate hinterlands, and far peripheries. Smaller centers exhibit greater household clustering compared to larger ones. This paper quantitatively assesses household clustering among nearly two dozen centers across the Maya Lowlands, linking environment and urban scale to settlement patterns. The findings are applicable to ancient societies and modern cities alike; understanding how humans form multi-scalar social groupings, such as neighborhoods, is fundamental to human experience and social organization.

Health-seeking behaviour of foreign workers in Singapore: Insights from emergency department visits.

INTRODUCTION: Foreign workers (FWs) on work permit face unique health challenges and potential barriers to healthcare. We aimed to examine the epidemiology, attendance patterns, disposition, and adherence to follow-up, by FWs on work permit to two emergency departments (EDs) in Singapore. METHODS: In this retrospective observational study, we included consecutive FWs on work permit who registered at the EDs of two public restructured hospitals from 1 May 2016 to 31 October 2016. Data obtained from electronic medical records included patient demographics, triage acuity, disposition, ED diagnoses and bill information. RESULTS: There were 6,429 individual FWs on work permit who contributed to 7,157 ED visits over the 6-month study period, with male predominance (72.7%, 4672/6429), and median age of 31 (interquartile range 26 to 38) years. A high proportion of these FWs were triaged to low-acuity status compared to the general ED population (66.9% versus 45.9%, P<0.001). Trauma-related injuries contributed to 34.4% of their visits, and were more likely to result in admission compared to non-trauma-related conditions (18.7% vs 15.2%, P<0.001). FWs engaged in shipyard, construction and process industries were more likely to be discharged "against medical advice" (14.8% vs 3.2%, P<0.001), and default their specialist outpatient follow-up (50.1% vs 34.2%, P<0.001) for non-trauma-related conditions compared to trauma-related injuries. CONCLUSION: In Singapore, the EDs of public restructured hospitals provide healthcare safety nets to FWs on work permit. These workers made more low-acuity visits compared to the general population during the study period and may face potential barriers to admission and follow-up.

Robust Performance of Potentially Functional SNPs in Machine Learning Models for the Prediction of Atorvastatin-Induced Myalgia.

Statins can cause muscle symptoms resulting in poor adherence to therapy and increased cardiovascular risk. We hypothesize that combinations of potentially functional SNPs (pfSNPs), rather than individual SNPs, better predict myalgia in patients on atorvastatin. This study assesses the value of potentially functional single nucleotide polymorphisms (pfSNPs) and employs six machine learning algorithms to identify the combination of SNPs that best predict myalgia. Methods: Whole genome sequencing of 183 Chinese, Malay and Indian patients from Singapore was conducted to identify genetic variants associated with atorvastatin induced myalgia. To adjust for confounding factors, demographic and clinical characteristics were also examined for their association with myalgia. The top factor, sex, was then used as a covariate in the whole genome association analyses. Variants that were highly associated with myalgia from this and previous studies were extracted, assessed for potential functionality (pfSNPs) and incorporated into six machine learning models. Predictive performance of a combination of different models and inputs were compared using the average cross validation area under ROC curve (AUC). The minimum combination of SNPs to achieve maximum sensitivity and specificity as determined by AUC, that predict atorvastatin-induced myalgia in most, if not all the six machine learning models was determined. Results: Through whole genome association analyses using sex as a covariate, a larger proportion of pfSNPs compared to non-pf SNPs were found to be highly associated with myalgia. Although none of the individual SNPs achieved genome wide significance in univariate analyses, machine learning models identified a combination of 15 SNPs that predict myalgia with good predictive performance (AUC >0.9). SNPs within genes identified in this study significantly outperformed SNPs within genes previously reported to be associated with myalgia. pfSNPs were found to be more robust in predicting myalgia, outperforming non-pf SNPs in the majority of machine learning models tested. Conclusion: Combinations of pfSNPs that were consistently identified by different machine learning models to have high predictive performance have good potential to be clinically useful for predicting atorvastatin-induced myalgia once validated against an independent cohort of patients.

Dockground Tool for Development and Benchmarking of Protein Docking Procedures.

Databases of protein-protein complexes are essential for the development of protein modeling/docking techniques. Such databases provide a knowledge base for docking algorithms, intermolecular potentials, search procedures, scoring functions, and refinement protocols. Development of docking techniques requires systematic validation of the modeling protocols on carefully curated benchmark sets of complexes. We present a description and a guide to the DOCKGROUND resource ( http://dockground.compbio.ku.edu ) for structural modeling of protein interactions. The resource integrates various datasets of protein complexes and other data for the development and testing of protein docking techniques. The sets include bound complexes, experimentally determined unbound, simulated unbound, model-model complexes, and docking decoys. The datasets are available to the user community through a Web interface.

Amnesia: a function of the temporal relation of footshock to electroconvulsive shock.

When rats received a brief footshock upon stepping off an elevated platform, and an electroconvulsive shock 30 seconds or 6 hours afterward, amnesia was not observed 24 hours later. If a second footshock (noncontingent) was delivered 0.5 second before the electroconvulsive shock, amnesia was observed. The amnesia was temporary if conditioning was strong and permanent if conditioning was weak.

Systemic cholinergic agents induce seizures and brain damage in lithium-treated rats.

Administration of pilocarpine or physostigmine to rats treated with lithium chloride produced sustained limbic seizures, widespread brain damage, and increased concentrations of D-myo-inositol-1-phosphate (a metabolite of the phosphoinositides, lipids involved in membrane receptor function) in the brain. The syndrome was preventable with atropine. The physostigmine doses and concentrations of blood lithium that caused the syndrome are similar to those considered appropriate for psychiatric chemotherapy.

Monitoring the time course of cerebral deoxyglucose metabolism by 31P nuclear magnetic resonance spectroscopy.

The phosphorylation of 2-deoxyglucose by the mammalian brain is used as an index of the brain's energy metabolism. The results of phosphorus-31 nuclear magnetic resonance (31P NMR) monitoring of conscious animals in vivo showed rapid phosphorylation of 2-deoxyglucose by brain tissue. The rate of phosphorylation as determined by 31P NMR was consistent with results achieved by tracer methods using carbon-14-labeled 2-deoxyglucose. However, the disappearance of 2-deoxyglucose-6-phosphate was shown to be faster than that reported by tracer studies and occurred without alterations of intracellular pH and energy homeostasis. These results were confirmed by gas chromatography and mass spectroscopy. It is postulated that 2-deoxyglucose may be metabolized in several ways, including dephosphorylation by a hexose phosphatase.

Advances in cataract surgery and intraocular lenses.

Cataract surgery is one of the most common medical procedures among persons age 65 and older. Once an inpatient procedure, it has become a simple outpatient surgery with extremely low rates of morbidity. With the development of implantable intraocular lenses (IOLs), patients undergoing cataract surgery gained the benefit of corrected pre-existing refractive error, astigmatism, and presbyopia. This article reviews developments in cataract surgery and describes current IOL technology.

Short-term aerobic exercise training in obese humans with type 2 diabetes mellitus improves whole-body insulin sensitivity through gains in peripheral, not hepatic insulin sensitivity.

CONTEXT: Short-term aerobic exercise training can improve whole-body insulin sensitivity in humans with type 2 diabetes mellitus; however, the contributions of peripheral and hepatic tissues to these improvements are not known. OBJECTIVE: Our objective was to determine the effect of 7-d aerobic exercise training on peripheral and hepatic insulin sensitivity during isoglycemic/hyperinsulinemic clamp conditions. DESIGN: Subjects were randomly assigned to one of two groups. The energy balance group consumed an isocaloric diet consisting of 50% carbohydrate, 30% fat, and 20% protein for 15 d. The energy balance plus exercise group consumed a similar diet over the 15 d and performed 50-min of treadmill walking at 70% of maximum oxygen consumption maximum during the second 7 d of the 15-d study period. Each subject underwent an initial isoglycemic/hyperinsulinemic clamp after 1-wk dietary control and a second clamp after completing the study. SETTING: The study was performed at Ohio State University's General Clinical Research Center. PARTICIPANTS: There were 18 obese, mildly diabetic humans included in the study. INTERVENTION: Aerobic exercise training was performed for 7 d. MAIN OUTCOME MEASURES: Whole-body, peripheral, and hepatic insulin sensitivity were measured. RESULTS: Exercise training did not have an impact on peripheral glucose uptake or endogenous glucose production during the basal state or low-dose insulin. Likewise, it did not alter endogenous glucose production during high-dose insulin. However, 1-wk of exercise training increased both whole-body (P<0.05) and peripheral insulin sensitivity (P<0.0001) during high-dose insulin. CONCLUSION: Improvements to whole body insulin sensitivity after short-term aerobic exercise training are due to gains in peripheral, not heptic insulin sensitivity.

Diacylglycerol accumulation and microvascular abnormalities induced by elevated glucose levels.

The present experiments were undertaken to examine the hypothesis that glucose-induced increased de novo synthesis of 1,2-diacyl-sn-glycerol (which has been observed in a number of different tissues, including retinal capillary endothelial cells exposed to elevated glucose levels in vitro) and associated activation of protein kinase C may play a role in mediating glucose-induced vascular functional changes. We report here that twice daily instillation of 30 mM glucose over 10 d in a rat skin chamber granulation tissue model induces approximately a 2.7-fold increase in diacylglycerol (DAG) levels (versus tissues exposed to 5 mM glucose) in association with marked increases in vascular clearance of albumin and blood flow. The glucose-induced increase in DAG levels as well as the vascular functional changes are prevented by addition of 3 mM pyruvate. Pharmacological activation of protein kinase C with the phorbol ester TPA in the presence of 5 mM glucose increases microvascular albumin clearance and blood flow, and similar effects are observed with 1-monoolein (MOG), a pharmacological inhibitor of the catabolism of endogenous DAG. A pharmacological inhibitor of protein kinase C (staurosporine) greatly attenuates the rise in microvascular albumin clearance (but not the rise in blood flow) induced by glucose or by MOG. These findings are compatible with the hypothesis that elevated concentrations of glucose increase tissue DAG content via de novo synthesis, resulting in protein kinase C activation, and that these biochemical events are among the factors that generate the increased microvascular albumin clearance.

Glucose-induced microvascular functional changes in nondiabetic rats are stereospecific and are prevented by an aldose reductase inhibitor.

Exposure of skin chamber granulation tissue vessels in nondiabetic rats to 11 or 15 mM D-glucose (but not L-glucose or 3-O-methylglucose) twice daily for 10 d induces vascular functional changes (increased albumin permeation and blood flow) identical to those in animals with mild or severe streptozotocin diabetes, respectively. These vascular changes are strongly linked to increased metabolism of glucose via the sorbitol pathway and are independent of nonenzymatic glycosylation as well as systemic metabolic and hormonal imbalances associated with the diabetic milieu. (J. Clin. Invest. 1990. 85:1167-1172.)

Effects of glucose on sorbitol pathway activation, cellular redox, and metabolism of myo-inositol, phosphoinositide, and diacylglycerol in cultured human retinal pigment epithelial cells.

Sorbitol (aldose reductase) pathway flux in diabetes perturbs intracellular metabolism by two putative mechanisms: reciprocal osmoregulatory depletion of other organic osmolytes e.g., myo-inositol, and alterations in NADPH/NADP+ and/or NADH/NAD+. The "osmolyte" and "redox" hypotheses predict secondary elevations in CDP-diglyceride, the rate-limiting precursor for phosphatidylinositol synthesis, but through different mechanisms: the "osmolyte" hypothesis via depletion of intracellular myo-inositol (the cosubstrate for phosphatidylinositol-synthase) and the "redox" hypothesis through enhanced de novo synthesis from triose phosphates. The osmolyte hypothesis predicts diminished phosphoinositide-derived arachidonyl-diacylglycerol, while the redox hypothesis predicts increased total diacylglycerol and phosphatidic acid. In high aldose reductase expressing retinal pigment epithelial cells, glucose-induced, aldose reductase inhibitor-sensitive CDP-diglyceride accumulation and inhibition of 32P-incorporation into phosphatidylinositol paralleled myo-inositol depletion (but not cytoplasmic redox, that was unaffected by glucose) and depletion of arachidonyl-diacylglycerol. 3 mM pyruvate added to the culture medium left cellular redox unaltered, but stimulated Na(+)-dependent myo-inositol uptake, accumulation, and incorporation into phosphatidylinositol. These results favor myo-inositol depletion rather than altered redox as the primary cause of glucose-induced aldose reductase-related defects in phospholipid metabolism in cultured retinal pigment epithelial cells.

Galactose ingestion increases vascular permeability and collagen solubility in normal male rats.

In view of the similarity of cataracts and neuropathy in galactose-fed and diabetic rats, the present experiments were undertaken to determine whether consumption of galactose-enriched diets (10, 25, or 50% by weight) also increases collagen crosslinking and permeation of vessels by 125I-albumin analogous to that observed in diabetic rats. The observations in these experiments: demonstrate that consumption of galactose-enriched diets for 3 wk selectively increases 125I-albumin permeation of the same vascular beds affected in diabetic rats and by diabetic vascular disease in humans (i.e., the aorta and vessels in the eye, kidney, sciatic nerve, and new tissue formed in the diabetic milieu); demonstrate that the susceptibility of the vasculature to aldose reductase-linked injury (increased permeability) varies greatly in different tissues; indicate that collagen solubility (crosslinking) changes in galactose-fed rats differ sharply from those in diabetic rats; and provide new evidence that consumption of galactose-enriched diets induces a hypogonadal state in male rats.

Importance of aerobic fitness in cardiovascular risks in sedentary overweight and obese African-American women.

BACKGROUND: Whether the level of aerobic fitness significantly impacts cardiovascular disease (CVD) risks in healthy, nondiabetic, overweight or obese African-American women remains uncertain. OBJECTIVE: To examine the clinical and metabolic risk factors of CVD in nondiabetic, sedentary overweight or obese African-American women with varying degrees of aerobic fitness. METHODS: Forty-eight African-American women, with mean age of 43 +/- 4.2 years and body mass index of 32.3 +/- 3.6 kg/m2, participated in the study. Fasting and 2-hr postprandial serum glucose, insulin, and C-peptide levels were obtained during oral glucose tolerance test. Insulin sensitivity was calculated by Homeostasis Model Assessment (HOMA-IR). Aerobic fitness was categorized empirically as very low aerobic fitness (VLAF; n = 17, VO2max < 21 ml/kg/min), low aerobic fitness (LAF; n = 12, between 21 and 24.4 ml/kg/min), and moderate aerobic fitness (MAF; n = 19, >24.4 ml/kg/min). RESULTS: Significant differences were found in serum glucose, insulin, and C-peptide levels, and HOMA-IR in the VLAF vs. LAF and MAF groups. Mean HOMA-IR was statistically greater in the VLAF and LAF when compared to MAF. Mean fasting serum cholesterol, triglycerides, and low-density lipoprotein cholesterol levels were higher in the VLAF group compared to the MAF group, whereas high-density lipoprotein cholesterol was lower in the VLAF group. Despite differences in the obesity indices and insulin resistance in the three groups, the atherogenic lipids and lipoproteins were within normal limits, irrespective of degree of VO2max. DISCUSSION: Modest aerobic fitness has significant impact on insulin sensitivity and atherogenic lipids and lipoprotein parameters and the overall risks for CVD in sedentary overweight or obese African-American women. Whether modest physical fitness translates into prevention of type 2 diabetes and CVD in African-American women remains to be determined.

Uveitis in the elderly: epidemiological data from the National Long-term Care Survey Medicare Cohort.

PURPOSE: There is a paucity of population-based data on the epidemiology of uveitis in the elderly. In the past 40 years, only 2 U.S. population-based studies have examined the epidemiology of uveitis. The conclusions of these studies on the burden of uveitis in the elderly differ greatly. In this analysis, we use Medicare claims data to define the population-based incidence and prevalence of uveitis in the United States elderly population. DESIGN: Cohort study. PARTICIPANTS: A cohort of 21644 Medicare beneficiaries drawn for the National Long-term Care Survey, a random sample of U.S. adults 65 years and older, was followed up from 1991 through 1999. METHODS: The International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes specific to uveitis were queried. To decrease the inclusion of uveitis caused by surgery, diagnoses occurring within 3 months of intraocular surgery were excluded. The incidence and prevalence of uveitis by anatomic location was calculated for each year in the study. MAIN OUTCOME MEASURES: The onset of uveitis during a given year and its presence in subsequent years. RESULTS: The cumulative yearly incidence of uveitis ranged from 302/100000 to 424/100000 persons per year and averaged 340.9/100000 persons per year. Anterior uveitis was the most common form of uveitis in this population, with a mean incidence of 243.6 cases per 100000 persons per year. The incidence of posterior uveitis averaged 76.6/100000 and the incidence of panuveitis/endophthalmitis averaged 41.7/100000. Only 2 cases of intermediate uveitis occurred during the study period. The cumulative prevalence of uveitis doubled from 511/100000 in 1991 to 1231/100000 in 1999, with anterior uveitis accounting for most prevalent cases in every year. CONCLUSIONS: The burden of uveitis in the elderly is substantial and is higher than previously thought. Longitudinal analysis of Medicare claims data may provide a useful tool for monitoring uncommon diseases, such as uveitis, in the elderly population.