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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.
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Inhibidores de la Angiogénesis , Bevacizumab , Inyecciones Intravítreas , Ranibizumab , Receptores de Factores de Crecimiento Endotelial Vascular , Proteínas Recombinantes de Fusión , Insuficiencia Renal , Factor A de Crecimiento Endotelial Vascular , Humanos , Receptores de Factores de Crecimiento Endotelial Vascular/administración & dosificación , Proteínas Recombinantes de Fusión/administración & dosificación , Proteínas Recombinantes de Fusión/efectos adversos , Ranibizumab/administración & dosificación , Ranibizumab/efectos adversos , Bevacizumab/administración & dosificación , Bevacizumab/efectos adversos , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/efectos adversos , Estudios Retrospectivos , Masculino , Femenino , Insuficiencia Renal/epidemiología , Insuficiencia Renal/complicaciones , Insuficiencia Renal/inducido químicamente , Incidencia , Anciano , Persona de Mediana Edad , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Retinopatía Diabética/tratamiento farmacológico , Retinopatía Diabética/epidemiología , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/complicaciones , Estudios de Seguimiento , Factores de Riesgo , Edema Macular/tratamiento farmacológico , Edema Macular/epidemiología , Edema Macular/diagnóstico , Oclusión de la Vena Retiniana/tratamiento farmacológico , Oclusión de la Vena Retiniana/diagnóstico , Oclusión de la Vena Retiniana/complicaciones , Oclusión de la Vena Retiniana/epidemiología , Ceguera/epidemiología , Ceguera/inducido químicamente , Ceguera/prevención & control , Ceguera/diagnóstico , Ceguera/etiologíaRESUMEN
Background: The Observational Health Data Sciences and Informatics (OHDSI) community has emerged as a leader in observational research on real-world clinical data for promoting evidence for healthcare and decision-making. The community has seen rapid growth in publications, citations, and the number of authors. Components of its successful uptake have been attributed to an open science and collaborative culture for research and development. Investigating the adoption of OHDSI as a field of study provides an opportunity to understand how communities embrace new ideas, onboard new members, and enhance their impact. Objective: To track, study, and evaluate an open scientific community's growth and impact. Method: We present a modern architecture leveraging open application programming interfaces to capture publicly available data (PubMed, YouTube, and EHDEN) on open science activities (publication, teaching, and engagement). Results: Three interactive dashboard were implemented for each publicly available artifact (PubMed, YouTube, and EHDEN). Each dashboard provides longitudinal summary analysis and has a searchable table, which differs in the available features related to each public artifact. Conclusion: We discuss the insights enabled by our approach to monitor the growth and impact of the OHDSI community by capturing artifacts of learning, teaching, and creation. We share the implications for different users based on their functional needs. As other scientific networks adopt open-source frameworks, our framework serves as a model for tracking the growth of their community, driving the perception of their development, engaging their members, and attaining higher impact.
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Background: SGLT2 inhibitors (SGLT2is) and GLP-1 receptor agonists (GLP1-RAs) reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). However, their effectiveness relative to each other and other second-line antihyperglycemic agents is unknown, without any major ongoing head-to-head trials. Methods: Across the LEGEND-T2DM network, we included ten federated international data sources, spanning 1992-2021. We identified 1,492,855 patients with T2DM and established cardiovascular disease (CVD) on metformin monotherapy who initiated one of four second-line agents (SGLT2is, GLP1-RAs, dipeptidyl peptidase 4 inhibitor [DPP4is], sulfonylureas [SUs]). We used large-scale propensity score models to conduct an active comparator, target trial emulation for pairwise comparisons. After evaluating empirical equipoise and population generalizability, we fit on-treatment Cox proportional hazard models for 3-point MACE (myocardial infarction, stroke, death) and 4-point MACE (3-point MACE + heart failure hospitalization) risk, and combined hazard ratio (HR) estimates in a random-effects meta-analysis. Findings: Across cohorts, 16·4%, 8·3%, 27·7%, and 47·6% of individuals with T2DM initiated SGLT2is, GLP1-RAs, DPP4is, and SUs, respectively. Over 5·2 million patient-years of follow-up and 489 million patient-days of time at-risk, there were 25,982 3-point MACE and 41,447 4-point MACE events. SGLT2is and GLP1-RAs were associated with a lower risk for 3-point MACE compared with DPP4is (HR 0·89 [95% CI, 0·79-1·00] and 0·83 [0·70-0·98]), and SUs (HR 0·76 [0·65-0·89] and 0·71 [0·59-0·86]). DPP4is were associated with a lower 3-point MACE risk versus SUs (HR 0·87 [0·79-0·95]). The pattern was consistent for 4-point MACE for the comparisons above. There were no significant differences between SGLT2is and GLP1-RAs for 3-point or 4-point MACE (HR 1·06 [0·96-1·17] and 1·05 [0·97-1·13]). Interpretation: In patients with T2DM and established CVD, we found comparable cardiovascular risk reduction with SGLT2is and GLP1-RAs, with both agents more effective than DPP4is, which in turn were more effective than SUs. These findings suggest that the use of GLP1-RAs and SGLT2is should be prioritized as second-line agents in those with established CVD. Funding: National Institutes of Health, United States Department of Veterans Affairs.
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Postmarket safety surveillance is an integral part of mass vaccination programs. Typically relying on sequential analysis of real-world health data as they accrue, safety surveillance is challenged by sequential multiple testing and by biases induced by residual confounding in observational data. The current standard approach based on the maximized sequential probability ratio test (MaxSPRT) fails to satisfactorily address these practical challenges and it remains a rigid framework that requires prespecification of the surveillance schedule. We develop an alternative Bayesian surveillance procedure that addresses both aforementioned challenges using a more flexible framework. To mitigate bias, we jointly analyze a large set of negative control outcomes that are adverse events with no known association with the vaccines in order to inform an empirical bias distribution, which we then incorporate into estimating the effect of vaccine exposure on the adverse event of interest through a Bayesian hierarchical model. To address multiple testing and improve on flexibility, at each analysis timepoint, we update a posterior probability in favor of the alternative hypothesis that vaccination induces higher risks of adverse events, and then use it for sequential detection of safety signals. Through an empirical evaluation using six US observational healthcare databases covering more than 360 million patients, we benchmark the proposed procedure against MaxSPRT on testing errors and estimation accuracy, under two epidemiological designs, the historical comparator and the self-controlled case series. We demonstrate that our procedure substantially reduces Type 1 error rates, maintains high statistical power and fast signal detection, and provides considerably more accurate estimation than MaxSPRT. Given the extensiveness of the empirical study which yields more than 7 million sets of results, we present all results in a public R ShinyApp. As an effort to promote open science, we provide full implementation of our method in the open-source R package EvidenceSynthesis.
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Sistemas de Registro de Reacción Adversa a Medicamentos , Vigilancia de Productos Comercializados , Vacunas , Humanos , Teorema de Bayes , Sesgo , Probabilidad , Vacunas/efectos adversosRESUMEN
Background: Electronic health records (EHRs) may help enable reliable, rapid data management for many uses, such as facilitating communication of advance care planning (ACP). However, issues with validity and accuracy of EHRs hinder the use of ACP information for practical applications. Design: We present a cross-sectional pilot study of 433 older adults with cancer from three large health care systems, participating in an ongoing multisite pragmatic trial (4UH3AG060626-02). We compared data extracted from dedicated structured EHR fields for ACP to a chart review of corresponding ACP documentation contained in the medical chart. Results: Structured ACP data existed for 43.2% of patients and varied by site (25.7% -48.9%). Of the identified structured ACP data elements, 59.2% of recorded elements were correct, 23.7% were incorrect, and 17.1% were duplicates with heterogeneity across sites. Conclusion: Structured ACP data in EHRs were frequently incorrect. This represents a problem for patients and their families, as well as quality improvement and research efforts. Clinical Trials Registration: NCT03609177.
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Planificación Anticipada de Atención , Registros Electrónicos de Salud , Anciano , Estudios Transversales , Documentación , Humanos , Proyectos PilotoRESUMEN
OBJECTIVE: Young adult (YA) cancer survivors who received gonadotoxic therapy are at risk for impaired fertility and/or childbearing difficulties. This study explored the experiences and financial concerns of survivors pursuing family building through assisted reproductive technology (ART) and adoption. METHODS: Retrospective study of data collected from grant applications for financial assistance with family building. Grounded theory methodology using an inductive data-driven approach guided qualitative data analysis. RESULTS: Participants (N = 46) averaged 32 years old (SD = 3.4) were primarily female (81%) and married/partnered (83%). Four main themes were identified representing the (1) emotional experiences and (2) financial barriers to family building after cancer, (3) perceived impact on partners, and (4) disrupted life trajectory. Negative emotions were pervasive but were balanced with hope and optimism that parenthood would be achieved. Still, the combination of high ART/adoption costs, the financial impact of cancer, and limited sources for support caused extreme financial stress. Further, in the face of these high costs, many survivors reported worry and guilt about burdening partners, particularly as couples failed to meet personal and societal expectations for parenthood timelines. CONCLUSION: After cancer, YAs face numerous psychosocial and financial difficulties in their pursuits of family building when ART/adoption is needed to achieve parenthood. Survivors interested in future children may benefit from follow-up fertility counseling post-treatment including discussion of ART options, surrogacy, and adoption, as appropriate, and potential barriers. Planning for the financial cost and burden in particular may help to avoid or mitigate financial stress later on.
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Supervivientes de Cáncer/psicología , Emociones , Fertilidad , Infertilidad/economía , Neoplasias/psicología , Técnicas Reproductivas Asistidas/economía , Estrés Psicológico , Adolescente , Adulto , Niño , Consejo , Femenino , Humanos , Infertilidad/psicología , Infertilidad/terapia , Masculino , Neoplasias/complicaciones , Neoplasias/terapia , Percepción , Técnicas Reproductivas Asistidas/psicología , Estudios Retrospectivos , Estrés Psicológico/economía , Estrés Psicológico/terapia , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: Survival and hospitalization are critically important outcomes considered when choosing between intensive hemodialysis (HD), conventional HD, and peritoneal dialysis (PD). However, the comparative effectiveness of these modalities is unclear. OBJECTIVE: We had the following aims: (1) to compare the association of mortality and hospitalization in patients undergoing intensive HD, compared with conventional HD or PD and (2) to appraise the methodological quality of the supporting evidence. DATA SOURCES: MEDLINE, Embase, ISI Web of Science, CENTRAL, and nephrology conference abstracts. STUDY ELIGIBILITY PARTICIPANTS AND INTERVENTIONS: We included cohort studies with comparator arm, and randomized controlled trials (RCTs) with >50% of adult patients (≥18 years) comparing any form of intensive HD (>4 sessions/wk or >5.5 h/session) with any form of chronic dialysis (PD, HD ≤4 sessions/wk or ≤5.5 h/session), that reported at least 1 predefined outcome (mortality or hospitalization). METHODS: We used the GRADE approach to systematic reviews and quality appraisal. Two reviewers screened citations and full-text articles, and extracted study-level data independently, with discrepancies resolved by consensus. We pooled effect estimates of randomized and observational studies separately using generic inverse variance with random effects models, and used fixed-effects models when only 2 studies were available for pooling. Predefined subgroups for the intensive HD cohorts were classified by nocturnal versus short daily HD and home versus in-center HD. RESULTS: Twenty-three studies with a total of 70 506 patients were included. Of the observational studies, compared with PD, intensive HD had a significantly lower mortality risk (hazard ratio [HR]: 0.67; 95% confidence interval [CI]: 0.53-0.84; I2 = 91%). Compared with conventional HD, home nocturnal (HR: 0.46; 95% CI: 0.38-0.55; I2 = 0%), in-center nocturnal (HR: 0.73; 95% CI: 0.60-0.90; I2 = 57%) and home short daily (HR: 0.54; 95% CI: 0.31-0.95; I2 = 82%) intensive regimens had lower mortality. Of the 2 RCTs assessing mortality, in-center short daily HD had lower mortality (HR: 0.54; 95% CI: 0.31-0.93), while home nocturnal HD had higher mortality (HR: 3.88; 95% CI: 1.27-11.79) in long-term observational follow-up. Hospitalization days per patient-year (mean difference: -1.98; 95% CI: -2.37 to -1.59; I2 = 6%) were lower in nocturnal compared with conventional HD. Quality of evidence was similarly low or very low in RCTs (due to imprecision) and observational studies (due to residual confounding and selection bias). LIMITATIONS: The overall quality of evidence was low or very low for critical outcomes. Outcomes such as quality of life, transplantation, and vascular access outcomes were not included in our review. CONCLUSIONS: Intensive HD regimens may be associated with reduced mortality and hospitalization compared with conventional HD or PD. As the quality of supporting evidence is low, patients who place a high value on survival must be adequately advised and counseled of risks and benefits when choosing intensive dialysis. Practice guidelines that promote shared decision-making are likely to be helpful.
CONTEXTE: Au moment de choisir une modalité de dialyse pour le traitement des patients souffrant d'insuffisance rénale, le taux de survie et la durée des hospitalisations sont des critères décisionnels d'une importance cruciale. Pourtant, l'efficacité différentielle de l'hémodialyse (HD) intensive, de l'HD conventionnelle et de la dialyse péritonéale (DP) demeure à ce jour mal connue. OBJECTIFS DE L'ÉTUDE: Nos objectifs allaient comme suit : 1) comparer le taux de mortalité et la durée des hospitalisations associés à chacune des modalités (HD intensive, HD conventionnelle et DP), et 2) évaluer la qualité méthodologique des données venant appuyer les résultats. SOURCES: Les données proviennent des bases de données en ligne MEDLINE, EMBASE et ISI Web of Science, de même que de CENTRAL et de résumés de conférence en néphrologie. ADMISSIBILITÉ À L'ÉTUDE PARTICIPANTS ET INTERVENTIONS: Ont été incluses à cette méta-analyse les études de cohorte comportant un volet comparatif et les essais contrôlés à répartition aléatoire comptant plus de 50 % de patients adultes et comparant n'importe quelle forme d'HD intensive (plus de 4 séances par semaine ou plus de 5,5 heures par séance) à n'importe quelle forme de dialyse chronique (DP ou HD à raison de 4 séances maximum par semaine ou de 5,5 heures maximum par séance). Les études retenues devaient également rapporter au moins un des deux critères décisionnels prédéfinis (mortalité et hospitalisation). MÉTHODOLOGIE: Nous avons employé l'approche GRADE (Grading of Recommendations Assessment, Development and Evaluation). Cette approche s'applique aux revues systématiques et à l'évaluation de la qualité des données. Deux personnes ont passé en revue des citations et des articles complets pour en extraire les données relatives à l'étude. Les divergences ont été résolues par consensus. Nous avons regroupé les différentes mesures provenant des essais à répartition aléatoire et des études observationnelles pour ensuite les analyser, de façon isolée, à l'aide de la méthode générique de l'inverse de la variance avec modèles à effet aléatoire. Pour les données où seules deux études étaient disponibles pour le regroupement des données, nous avons plutôt employé la méthode générique de l'inverse de la variance avec modèles à effet fixe. Des sous-groupes avaient été prédéfinis dans les cohortes de patients traités par HD intensive, selon le moment (de jour ou de nuit) et le lieu (en centre de dialyse ou à domicile) du traitement. RÉSULTATS: Cette méta-analyse compte 23 études totalisant 70 506 patients. Selon les études observationnelles, lorsque comparée à la DP, l'HD intensive était corrélée à un risque de mortalité significativement plus faible (HR=0,67; IC 95 0,53-0,84; I2=91 %). En comparaison avec l'HD conventionnelle, les schémas de traitement par HD intensive nocturne prodiguée à domicile (HR=0,46; IC 95 : 0,38-0,55; I2=0 %), nocturne en centre (HR=0,73; IC 95 : 0,60-0,90; I2=57 %) et de courte durée, de jour, à domicile (HR=0,54; IC 95 : 0,31-0,95; I2=82%) étaient corrélées à de plus faibles taux de mortalité. Des deux essais contrôlés à répartition aléatoire qui faisaient mention du taux de mortalité, l'HD diurne de courte durée en centre présentait le plus faible taux de mortalité (HR=0,54; IC 95 : 0,31-0,93) alors que l'HD nocturne à domicile présentait le taux de mortalité le plus élevé (HR=3,88; IC 95 : 1,27-11,79) selon les suivis observationnels faits à long terme. Le nombre de jours d'hospitalisation par année-patient (différence moyenne = -1,98 an; IC 95 : -1,59 à 2,37; I2=6 %) était plus faible chez les patients traités par HD intensive nocturne en comparaison avec ceux qui suivaient un traitement par la méthode conventionnelle. Dans tous les cas, la qualité des données recueillies s'est avérée faible ou très faible, qu'il s'agisse d'essais contrôlés à répartition aléatoire (en raison de l'imprécision) ou d'études observationnelles (en raison de facteurs de confusion et de biais de sélection). LIMITES DE L'ÉTUDE: Dans l'ensemble, la qualité des données recueillies pour appuyer les critères décisionnels jugés essentiels s'est avérée faible ou très faible. De plus, des éléments tels que la qualité de vie du patient, la greffe et les enjeux liés à l'accès vasculaire n'ont pas été pris en compte dans notre revue systématique. CONCLUSION: Le traitement de l'insuffisance rénale par HD intensive pourrait être associé à un taux de mortalité réduit et à des séjours à l'hôpital écourtés en comparaison avec les traitements par HD conventionnelle ou par DP. Cependant, en raison de la piètre qualité des données appuyant ces résultats, les patients qui accordent une grande importance à la survie devraient être adéquatement informés et conseillés sur les risques et les bienfaits offerts par l'HD intensive comme modalité de traitement. L'application de lignes directrices concernant la prise de décision conjointe en pratique clinique pourrait être pertinente.