Similar Risk of Kidney Failure among Patients with Blinding Diseases Who Receive Ranibizumab, Aflibercept, and Bevacizumab: An Observational Health Data Sciences and Informatics Network Study.

PURPOSE: To characterize the incidence of kidney failure associated with intravitreal anti-VEGF exposure; and compare the risk of kidney failure in patients treated with ranibizumab, aflibercept, or bevacizumab. DESIGN: Retrospective cohort study across 12 databases in the Observational Health Data Sciences and Informatics (OHDSI) network. SUBJECTS: Subjects aged ≥ 18 years with ≥ 3 monthly intravitreal anti-VEGF medications for a blinding disease (diabetic retinopathy, diabetic macular edema, exudative age-related macular degeneration, or retinal vein occlusion). METHODS: The standardized incidence proportions and rates of kidney failure while on treatment with anti-VEGF were calculated. For each comparison (e.g., aflibercept versus ranibizumab), patients from each group were matched 1:1 using propensity scores. Cox proportional hazards models were used to estimate the risk of kidney failure while on treatment. A random effects meta-analysis was performed to combine each database's hazard ratio (HR) estimate into a single network-wide estimate. MAIN OUTCOME MEASURES: Incidence of kidney failure while on anti-VEGF treatment, and time from cohort entry to kidney failure. RESULTS: Of the 6.1 million patients with blinding diseases, 37 189 who received ranibizumab, 39 447 aflibercept, and 163 611 bevacizumab were included; the total treatment exposure time was 161 724 person-years. The average standardized incidence proportion of kidney failure was 678 per 100 000 persons (range, 0-2389), and incidence rate 742 per 100 000 person-years (range, 0-2661). The meta-analysis HR of kidney failure comparing aflibercept with ranibizumab was 1.01 (95% confidence interval [CI], 0.70-1.47; P = 0.45), ranibizumab with bevacizumab 0.95 (95% CI, 0.68-1.32; P = 0.62), and aflibercept with bevacizumab 0.95 (95% CI, 0.65-1.39; P = 0.60). CONCLUSIONS: There was no substantially different relative risk of kidney failure between those who received ranibizumab, bevacizumab, or aflibercept. Practicing ophthalmologists and nephrologists should be aware of the risk of kidney failure among patients receiving intravitreal anti-VEGF medications and that there is little empirical evidence to preferentially choose among the specific intravitreal anti-VEGF agents. FINANCIAL DISCLOSURES: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

An estimate of missed pediatric sepsis in the emergency department.

BACKGROUND: Timely diagnosis of pediatric sepsis remains elusive. We estimated the risk of potentially missed pediatric sepsis in US emergency departments (EDs) and determined factors associated with its occurrence. METHODS: In a retrospective study of linked inpatient and ED records from four states using administrative data (excluding 40% with missing identifiers), we identified children admitted with severe sepsis and/or septic shock who had at least one ED treat-and-release visit in the 7 days prior to sepsis admission. An expert panel rated the likelihood of each ED visit being related to subsequent sepsis admission. We used multivariable regression to identify associations with potentially missed sepsis. RESULTS: Of 1945 patients admitted with severe sepsis/septic shock, 158 [8.1%; 95% confidence interval (CI), 6.9%-9.4%] had potentially missed sepsis during an antecedent treat-and-release ED visit. The odds of potentially missed sepsis were lower for each additional comorbid chronic condition [odds ratio (OR), 0.86; 95% CI, 0.80-0.92] and higher in California (OR, 2.26; 95% CI, 1.34-3.82), Florida (OR, 3.33; 95% CI, 1.95-5.70), and Massachusetts (OR, 2.87; 95% CI, 1.35-6.09), compared to New York. CONCLUSIONS: Administrative data can be used to screen large populations for potentially missed sepsis and identify cases that warrant detailed record review.

Ecological Networks over the Edge: Hypergraph Trait-Mediated Indirect Interaction (TMII) Structure.

Analyses of ecological network structure have yielded important insights into the functioning of complex ecological systems. However, such analyses almost universally omit non-pairwise interactions, many classes of which are crucial for system structure, function, and resilience. Hypergraphs are mathematical constructs capable of considering such interactions: we discuss their utility for studying ecological networks containing diverse interaction types, and associated challenges and strategies. We demonstrate the approach using a real-world coffee agroecosystem in which resistance to agricultural pests depends upon a large number of TMIIs. A hypergraph representation successfully reflects both the importance of species imposing such effects and the context-dependency of that importance in terms of how it is affected by removal of other species from the system.