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Given a closed, convex set X\subseteq \bbR n , containing the origin, we consider the problem (P) : max {c^\T x\colon x ∈ X} . We show that, for a fixed dimension, n , and fixed \eps , 0 <\eps<1 , the existence of a combinatorial, strongly polynomial \eps -approximation separation algorithm for the set X is equivalent to the existence of a combinatorial, strongly polynomial \eps -approximation optimization algorithm for the problem (P) . [ABSTRACT FROM AUTHOR]

Background: Fabry disease (FD) is an X-linked lysosomal storage disorder caused by deficient α-galactosidase A activity. The spectrum of disease includes phenotypes ranging from "classic" to "later-onset," with varying kidney disease progression. Identifying patterns of declining kidney function and involvement of other major organs in patients with FD is important to guide therapy decisions., Methods: Clusters of patients with FD and similar estimated glomerular filtration rate (eGFR) decline and age were created using agglomerative clustering of data captured between 2007 and 2020 in the United States Optum Market Clarity database. Male patients with a diagnosis of FD and two or more eGFR values ≥6 months apart were included. Disease progression was compared with a control cohort of patients without an FD diagnosis., Results: eGFR values from 234 male patients with FD were analysed, yielding seven clusters. Five clusters demonstrated disease progression from "natural" eGFR decline, with a slight decrease in kidney function and eGFR usually within the normal range, to rapid, early decline in eGFR and cardiac complications. When compared with the control cohort, a more rapid decline and a higher percentage of cardiac hypertrophy, heart failure, arrhythmias and stroke were noted in the study group. An inflection point was observed in each cluster when deterioration of kidney function accelerated., Conclusions: Clustering of male patients with FD by decline in kidney function, organ involvement and phenotype through analysis of real-world data provides a reference that could help determine the optimal time for initiation of FD-specific treatment and facilitate management decisions made by healthcare professionals., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)

Background: Sotalol and dronedarone are both used for maintenance of sinus rhythm for patients with atrial fibrillation. However, while sotalol requires initial monitoring for QT prolongation and proarrhythmia, dronedarone does not. These treatments can be used in comparable patients, but their safety and effectiveness have not been compared head to head. Therefore, we retrospectively evaluated the effectiveness and safety using data from a large health care system., Methods: Using Veterans Health Administration data, we identified 11 296 antiarrhythmic drug-naive patients with atrial fibrillation prescribed dronedarone or sotalol in 2012 or later. We excluded patients with prior conduction disease, pacemakers or implantable cardioverter-defibrillators, ventricular arrhythmia, cancer, renal failure, liver disease, or heart failure. We used natural language processing to identify and compare baseline left ventricular ejection fraction between treatment arms. We used 1:1 propensity score matching, based on patient demographics, comorbidities, and medications, and Cox regression to compare strategies. To evaluate residual confounding, we performed falsification analysis with nonplausible outcomes., Results: The matched cohort comprised 6212 patients (3106 dronedarone and 3106 sotalol; mean [±SD] age, 71±10 years; 2.5% female; mean [±SD] CHA 2 DS 2 -VASC, 2±1.3). The mean (±SD) left ventricular ejection fraction was 55±11 and 58±10 for dronedarone and sotalol users, correspondingly. Dronedarone, compared with sotalol, did not demonstrate a significant association with risk of cardiovascular hospitalization (hazard ratio, 1.03 [95% CI, 0.88-1.21]) or all-cause mortality (hazard ratio, 0.89 [95% CI, 0.68-1.16]). However, dronedarone was associated with significantly lower risk of ventricular proarrhythmic events (hazard ratio, 0.53 [95% CI, 0.38-0.74]) and symptomatic bradycardia (hazard ratio, 0.56 [95% CI, 0.37-0.87]). The primary findings were stable across sensitivity analyses. Falsification analyses were not significant., Conclusions: Dronedarone, compared with sotalol, was associated with a lower risk of ventricular proarrhythmic events and conduction disorders while having no difference in risk of incident cardiovascular hospitalization and mortality. These observational data provide the basis for prospective efficacy and safety trials., Competing Interests: Disclosures Dr Pundi reports research grants from the American Heart Association and the American College of Cardiology and is a consultant for Evidently and 100Plus. Dr Kabadi is an employee and shareholder at Sanofi. Dr Blomström-Lundqvist reports personal fees from Bayer, Medtronic, CathPrint, Octopus, Sanofi Aventis, Boston Sci, Merck Sharp & Dohme, Abbotts, and Philips. Dr John Camm reports personal fees from Bayer, Daiichi Sankyo, Pfizer/BMS, Medtronic Abbott, Boston Scientific, Menarini, and Sanofi. Dr Kowey is an ad hoc consultant for Sanofi. Dr Singh is a consultant for Abbott, Biotronik, Boston Sci, Cardiologs, Medtronic, Implicity, Cardiac Rhythm Group, Sanofi, EBR, Microport, Biosense Webster, Sanofi, and Orchestra BioMed. Dr Rashkin is an employee at Sanofi. Dr Wieloch is an employee and shareholder at Sanofi. Dr Turakhia reports research grants from Bristol Myers Squibb, American Heart Association, Apple, Inc, Bayer, and the Food and Drug Administration and is a consultant for Medtronic, Abbott, Biotronik, Sanofi, Pfizer, Myokardia, Johnson & Johnson, Milestone, InCarda, 100Plus, Alivecor, Acutus Medical, and BrightInsight. Dr Sandhu reports research grant 1K23HL151672-01 from the National Heart, Lung, and Blood Institute. The other authors report no conflicts.

Problem: Ambiguity in communication of key study parameters limits the utility of real-world evidence (RWE) studies in healthcare decision-making. Clear communication about data provenance, design, analysis, and implementation is needed. This would facilitate reproducibility, replication in independent data, and assessment of potential sources of bias., What We Did: The International Society for Pharmacoepidemiology (ISPE) and ISPOR-The Professional Society for Health Economics and Outcomes Research (ISPOR) convened a joint task force, including representation from key international stakeholders, to create a harmonized protocol template for RWE studies that evaluate a treatment effect and are intended to inform decision-making. The template builds on existing efforts to improve transparency and incorporates recent insights regarding the level of detail needed to enable RWE study reproducibility. The overarching principle was to reach for sufficient clarity regarding data, design, analysis, and implementation to achieve 3 main goals. One, to help investigators thoroughly consider, then document their choices and rationale for key study parameters that define the causal question (e.g., target estimand), two, to facilitate decision-making by enabling reviewers to readily assess potential for biases related to these choices, and three, to facilitate reproducibility., Strategies to Disseminate and Facilitate Use: Recognizing that the impact of this harmonized template relies on uptake, we have outlined a plan to introduce and pilot the template with key international stakeholders over the next 2 years., Conclusion: The HARmonized Protocol Template to Enhance Reproducibility (HARPER) helps to create a shared understanding of intended scientific decisions through a common text, tabular and visual structure. The template provides a set of core recommendations for clear and reproducible RWE study protocols and is intended to be used as a backbone throughout the research process from developing a valid study protocol, to registration, through implementation and reporting on those implementation decisions., (© 2022 The Authors. Pharmacoepidemiology and Drug Safety published by John Wiley & Sons Ltd.)

Objectives: Ambiguity in communication of key study parameters limits the utility of real-world evidence (RWE) studies in healthcare decision-making. Clear communication about data provenance, design, analysis, and implementation is needed. This would facilitate reproducibility, replication in independent data, and assessment of potential sources of bias., Methods: The International Society for Pharmacoepidemiology (ISPE) and ISPOR-The Professional Society for Health Economics and Outcomes Research (ISPOR) convened a joint task force, including representation from key international stakeholders, to create a harmonized protocol template for RWE studies that evaluate a treatment effect and are intended to inform decision-making. The template builds on existing efforts to improve transparency and incorporates recent insights regarding the level of detail needed to enable RWE study reproducibility. The over-arching principle was to reach for sufficient clarity regarding data, design, analysis, and implementation to achieve 3 main goals. One, to help investigators thoroughly consider, then document their choices and rationale for key study parameters that define the causal question (e.g., target estimand), two, to facilitate decision-making by enabling reviewers to readily assess potential for biases related to these choices, and three, to facilitate reproducibility., Strategies to Disseminate and Facilitate Use: Recognizing that the impact of this harmonized template relies on uptake, we have outlined a plan to introduce and pilot the template with key international stakeholders over the next 2 years., Conclusion: The HARmonized Protocol Template to Enhance Reproducibility (HARPER) helps to create a shared understanding of intended scientific decisions through a common text, tabular and visual structure. The template provides a set of core recommendations for clear and reproducible RWE study protocols and is intended to be used as a backbone throughout the research process from developing a valid study protocol, to registration, through implementation and reporting on those implementation decisions., (Copyright © 2022. Published by Elsevier Inc.)

Disappearing nail bed (DNB) is a condition characterized by irreversible epithelialization of the nail bed following long-standing onycholysis. This phenomenon can occur in fingernails and toenails. Factors implicated in the development of DNB include trauma, manicuring, and onychotillomania and dermatologic conditions like psoriasis and dermatitis. Specifically for the toenail, contributing factors also include increasing age, history of trauma, surgery, onychomycosis, and onychogryphosis. A grading system that stages the progression of onycholysis to DNB has been proposed to aid clinicians in the diagnosis and treatment of these conditions. Several methods have been designated for the treatment of DNB., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: In 2014, the ASCO developed CancerLinQ (CLQ), a health technology platform for oncology. The CLQ Discovery (CLQD) database was created to make data available for research and this paper provides a summary of this database., Methods: This study described the clinical and demographic characteristics of the 12 most common cancers in the CLQD database. We included patients with a new malignant tumor diagnosis between January 1, 2013, and December 31, 2018, of the following cancers: breast, lung and bronchus, prostate, colon and rectum, melanoma of the skin, bladder, non-Hodgkin lymphoma, kidney and renal pelvis, uterus, leukemia, pancreas, and thyroid. Patients with an in-situ diagnosis were excluded. Summary statistics and Kaplan-Meier survival estimates were calculated for each tumor., Results: From 2013 to 2018, 491,360 patients were diagnosed with the study tumors. Breast cancer (139,506) was the most common, followed by lung and bronchus (70,959), prostate (63,303), and colon and rectum (53,504). The median age at diagnosis (years) was 61, 68, 68, and 64 in breast, lung and bronchus, prostate, and colon and rectum cohorts, respectively. Compared to the SEER 5-year overall survival estimates for several tumor types were higher in the CLQD database, possibly because of incomplete mortality capture in electronic health records., Conclusion: This paper presents the first description of the CLQD database since its inception. CLQ will continue to evolve over time, and the breadth and depth of this data asset will continue to grow. ASCO and CLQ's long-term goal is to improve the quality of patient care and create a sustainable database for oncology researchers. These results demonstrate that CLQ built a scalable database that can be used for oncology research., Competing Interests: Danielle M. PotterEmployment: AstraZenecaStock and Other Ownership Interests: AstraZenecaResearch Funding: AstraZenecaTravel, Accommodations, Expenses: AstraZenecaOther Relationship: Tempus, Concerto HealthAI Aliki TaylorEmployment: AstraZeneca, TakedaStock and Other Ownership Interests: AstraZenecaTravel, Accommodations, Expenses: AstraZeneca Cathy EmmasEmployment: AstraZenecaStock and Other Ownership Interests: AstraZeneca Shaum KabadiEmployment: AstraZeneca, SanofiStock and Other Ownership Interests: AstraZeneca Miao JiangEmployment: AstraZeneca, Vanda PharmaceuticalsStock and Other Ownership Interests: AstraZeneca, Vanda PharmaceuticalsNo other potential conflicts of interest were reported.

Purpose: This paper describes the approach used to develop the Adolescent Family Life Program (AFLP) Positive Youth Development (PYD) Model within the structure of an existing state government-run program., Description: The California Department of Public Health, Maternal, Child and Adolescent Health (CDPH/MCAH) Division undertook an innovative approach to develop a program model to help expectant and parenting youth build resilience. CDPH/MCAH started by assessing existing program efforts and theory to develop and test new strategies in the field, structure a program model, and build toward broader expansion and sustainability. CDPH/MCAH engaged local organizations from across the state, their staff and enrolled youth, experts, and evaluators in an iterative program development process to standardize an effective model that could be replicated and evaluated., Assessment: Key lessons for program developers and administrators are to ensure adequate staffing with diverse expertise related to the topic and content to support the multiple components of program development and implementation, evaluation, and training; identify the guiding theory and framework early and link them with clearly articulated core components to ensure the final model reflects the intended purpose and is structured to support implementation; engage implementation staff on the ground and focus early and often on processes for supporting people through change., Conclusion: The lessons learned can guide others working with existing programs to develop standardized program models or translate new science and theory into practice.

Purpose: Existing studies evaluating patient adherence to oral targeted therapies such as tyrosine kinase inhibitors focus on small populations with single malignancies. This study evaluated patterns of use of oral agents in a larger population across multiple hematologic malignancies., Methods: Adult patients diagnosed with a hematologic malignancy and prescribed oral targeted therapy between 2011 and 2016 ( N  = 18,976) were identified from the MarketScan Commercial Claims and Encounters, and Medicare Supplemental databases. Eligible patients were enrolled in monthly prescription plans 6 months before and 12 months after the index date (date of first prescription claim; n  = 2442). Multivariable logistic regressions were used to determine predictors of adherence using the medication possession ratio (MPR) and persistence through prescription refill gaps., Results: The overall median adherence was 0.9 (MPR ≥ 80%) and was comparable between once-daily (QD) and twice-daily (BID) groups. Overall, 59% of patients were persistent at 12 months. Patients on QD and BID products did not have any significant differences in adherence (fixed-interval MPR, odds ratio 0.94; 95% confidence interval (CI), 0.75-1.18) or persistence (odds ratio 0.93; 95% CI, 0.75-1.17) 12 months from index. Significant predictors of adherence and persistence included patient age, total inpatient admissions, number of adverse events, and total hospital visits., Conclusion: Patient-specific clinical factors, rather than regimen-specific factors, were the main predictors of oral targeted therapy adherence and persistence. Adherence to oral targeted therapies appears to be similar for patients on QD and BID regimens in the real-world setting.

Aim: To estimate budget impact of adopting lesinurad as add-on to allopurinol for urate-lowering therapy in gout. Methods: A budget impact model was developed for a US payer perspective, using a Markov model to estimate costs, survival and discontinuation in a one-million-member health plan. The population included patients failing first-line gout therapy, followed for 5 years. Results: Incremental costs of adding lesinurad versus no lesinurad were US$241,907 and US$1,098,220 in first and fifth years, respectively. Cumulative 5-year incremental cost was US$3,633,440. Estimated incremental mean cost per treated patient with gout per year was US$112. The mean per-member per-month cost increased by US$0.06. Conclusion: Initiating lesinurad would result in an incremental per-member per-month cost of US$0.06 over 5 years.

Background: Anemia is common in non-dialysis-dependent chronic kidney disease (NDD-CKD) patients, but detailed information on prevalence and treatment is lacking., Methods: We evaluated anemia prevalence and treatment using two datasets: the Medicare 20% random sample (ages 66-85 years), and the Truven Health MarketScan database (ages 18-63 years). We selected stage 3-5 NDD-CKD patients with and without anemia from both databases during 2011-2013. We evaluated anemia prevalence and treatment (erythropoietin stimulating agents [ESAs], intravenous [IV] iron, red blood cell [RBC] transfusions) following anemia diagnosis during a 1-year baseline period, and healthcare utilization during a 1-year follow-up period. We used Poisson regression models to compare healthcare utilization in patients with and without anemia, adjusting for demographics, baseline comorbid conditions, inflammatory conditions, and CKD stage., Results: We identified 218,079 older and 56,188 younger stage 3-5 NDD-CKD patients. Anemia prevalence increased with age in both datasets; was higher in women, black patients (Medicare only), and patients with comorbid conditions; and rose sharply with increasing CKD stage. Of 15,716 younger anemic patients, 11.7%, 10.8%, and 9.4% were treated with RBC transfusion, ESAs, and IV iron, respectively. Corresponding proportions of 109,251 older anemic patients were 22.2%, 12.7%, and 6.7%. Regardless of age, anemic patients were more likely than non-anemic patients to use healthcare resources, including hospitalizations and emergency department, hematologist, nephrologist, and outpatient visits. Anemic NDD-CKD patients were more likely to be treated with RBC transfusion than with ESAs or IV iron., Conclusion: More research is necessary to determine best approaches to anemia management in CKD.

Background and Purpose: Middle ear space is one of the most important components of the Jahrsdoerfer grading system (J-score), which is used to determine surgical candidacy for congenital aural atresia. The purpose of this study was to introduce a semiautomated method for measuring middle ear volume and determine whether middle ear volume, either alone or in combination with the J-score, can be used to predict early postoperative audiometric outcomes., Materials and Methods: A retrospective analysis was conducted of 18 patients who underwent an operation for unilateral congenital aural atresia at our institution. Using the Livewire Segmentation tool in the Carestream Vue PACS, we segmented middle ear volumes using a semiautomated method for all atretic and contralateral normal ears on preoperative high-resolution CT imaging. Postsurgical audiometric outcome data were then analyzed in the context of these middle ear volumes., Results: Atretic middle ear volumes were significantly smaller than those in contralateral normal ears ( P < .001). Patients with atretic middle ear volumes of >305 mm 3 had significantly better postoperative pure tone average and speech reception thresholds than those with atretic ears below this threshold volume ( P = .01 and P = .006, respectively). Atretic middle ear volume incorporated into the J-score offered the best association with normal postoperative hearing (speech reception threshold ≤ 30 dB; OR = 37.8, P = .01)., Conclusions: Middle ear volume, calculated in a semiautomated fashion, is predictive of postsurgical audiometric outcomes, both independently and in combination with the conventional J-score., (© 2018 by American Journal of Neuroradiology.)

Background: Neuropsychological changes that may occur due to the environmental and psychological stressors of prolonged spaceflight motivated the development of the Cognition Test Battery. The battery was designed to assess multiple domains of neurocognitive functions linked to specific brain systems. Tests included in Cognition have been validated, but not in high-performing samples comparable to astronauts, which is an essential step toward ensuring their usefulness in long-duration space missions., Methods: We administered Cognition (on laptop and iPad) and the WinSCAT, counterbalanced for order and version, in a sample of 96 subjects (50% women; ages 25-56 yr) with at least a Master's degree in science, technology, engineering, or mathematics (STEM). We assessed the associations of age, sex, and administration device with neurocognitive performance, and compared the scores on the Cognition battery with those of WinSCAT. Confirmatory factor analysis compared the structure of the iPad and laptop administration methods using Wald tests., Results: Age was associated with longer response times (mean β = 0.12) and less accurate (mean β = -0.12) performance, women had longer response times on psychomotor (β = 0.62), emotion recognition (β = 0.30), and visuo-spatial (β = 0.48) tasks, men outperformed women on matrix reasoning (β = -0.34), and performance on an iPad was generally faster (mean β = -0.55). The WinSCAT appeared heavily loaded with tasks requiring executive control, whereas Cognition assessed a larger variety of neurocognitive domains., Discussion: Overall results supported the interpretation of Cognition scores as measuring their intended constructs in high performing astronaut analog samples.Moore TM, Basner M, Nasrini J, Hermosillo E, Kabadi S, Roalf DR, McGuire S, Ecker AJ, Ruparel K, Port AM, Jackson CT, Dinges DF, Gur RC. Validation of the Cognition Test Battery for spaceflight in a sample of highly educated adults. Aerosp Med Hum Perform. 2017; 88(10):937-946.

Background: The connection between Alzheimer's disease (AD) and olfactory deficits is well documented and further, alterations in olfactory functioning may signal declines in functions associated with dementia. The aim of the present comprehensive meta-analysis was to investigate the nature of olfactory deficits in mild cognitive impairment (MCI)., Methods: Articles were identified through computerised literature search from inception to 30 June 2016 using PubMed, MEDLINE and PsychInfo databases. In order to control for differences in sample size during effect size computation, studies were weighted according to their inverse variance estimates., Results: 31 articles (62 effects) were identified, which included 1993 MCI patients and 2861 healthy older adults (HOA). Included studies contrasted odour identification, discrimination, detection threshold and/or memory between cases and controls. Moderate to large and heterogeneous effects were seen for olfactory deficits in MCI relative to HOA (d=-0.76, 95% CI -0.87<δ<-0.64). Moderator analysis revealed that tests of odour identification yielded larger effect sizes than those of odour detection threshold or memory. In addition, a potential interaction between age and sex was observed, with male patients carrying a larger burden of olfactory deficit and older female patients performing better on olfactory tests., Conclusions and Relevance: Olfactory deficits are present and robust in MCI. Odour identification is most impaired in MCI, which parallels the most prominent sensory deficit seen in AD. As such, a simple-to-administer test of odour identification warrants inclusion in the screening of individuals at risk for developing AD., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Background: Opportunities to leverage observational data for precision medicine research are hampered by underlying sources of bias and paucity of methods to handle resulting uncertainty. We outline an approach to account for bias in identifying comorbid associations between 2 rare genetic disorders and type 2 diabetes (T2D) by applying a positive and negative control disease paradigm., Research Design: Association between 10 common and 2 rare genetic disorders [Hereditary Fructose Intolerance (HFI) and α-1 antitrypsin deficiency] and T2D was compared with the association between T2D and 7 negative control diseases with no established relationship with T2D in 4 observational databases. Negative controls were used to estimate how much bias and variance existed in datasets when no effect should be observed., Results: Unadjusted association for common and rare genetic disorders and T2D was positive and variable in magnitude and distribution in all 4 databases. However, association between negative controls and T2D was 200% greater than expected indicating the magnitude and confidence intervals for comorbid associations are sensitive to systematic bias. A meta-analysis using this method demonstrated a significant association between HFI and T2D but not for α-1 antitrypsin deficiency., Conclusions: For observational studies, when covariate data are limited or ambiguous, positive and negative controls provide a method to account for the broadest level of systematic bias, heterogeneity, and uncertainty. This provides greater confidence in assessing associations between diseases and comorbidities. Using this approach we were able to demonstrate an association between HFI and T2D. Leveraging real-world databases is a promising approach to identify and corroborate potential targets for precision medicine therapies.

Background: Measurements of olfaction may serve as useful biomarkers of incipient dementia. Here we examine the improvement in diagnostic accuracy of Alzheimer's disease (AD) and mild cognitive impairment (MCI) when assessing both cognitive functioning and odor identification., Objective: To determine the utility of odor identification as a supplementary screening test in incipient AD., Methods: Sniffin' Sticks Odor Identification Test (SS-OIT) and the Montreal Cognitive Assessment (MoCA) were administered in 262 AD, 174 MCI [150 amnestic (aMCI), and 24 non-amnestic (naMCI)], and 292 healthy older adults (HOA)., Results: Odor identification scores were higher in HOA relative to MCI or AD groups, and MCI outperformed AD. Odor identification scores were higher in aMCI single domain than aMCI multiple domain. Complementing MoCA scores with the SS-OIT significantly improved diagnostic accuracy of individuals with AD and MCI, including within MCI subgroups., Discussion: Odor identification is a useful supplementary screening tool that provides additional information relevant for clinical categorization of AD and MCI, including those who are at highest risk to convert to AD.

Introduction: Screening for cognitive deficits is essential in neurodegenerative disease. Screening tests, such as the Montreal Cognitive Assessment (MoCA), are easily administered, correlate with neuropsychological performance and demonstrate diagnostic utility. Yet, administration time is too long for many clinical settings., Methods: Item response theory and computerised adaptive testing simulation were employed to establish an abbreviated MoCA in 1850 well-characterised community-dwelling individuals with and without neurodegenerative disease., Results: 8 MoCA items with high item discrimination and appropriate difficulty were identified for use in a short form (s-MoCA). The s-MoCA was highly correlated with the original MoCA, showed robust diagnostic classification and cross-validation procedures substantiated these items., Discussion: Early detection of cognitive impairment is an important clinical and public health concern, but administration of screening measures is limited by time constraints in demanding clinical settings. Here, we provide as-MoCA that is valid across neurological disorders and can be administered in approximately 5 min., Competing Interests: Conflicts of Interest: None declared., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.)

Context: The relationship between rising body mass index (BMI) and prospective risk of nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) is virtually absent., Objective: Determine the extent of the association between BMI and risk of future NAFLD diagnosis, stratifying by sex and diabetes., Design: Two prospective studies using Humedica and Health Improvement Network (THIN) with 1.54 and 4.96 years of follow-up, respectively., Setting: Electronic health record databases., Participants: Patients with a recorded BMI measurement between 15 and 60 kg/m(2), and smoking status, and 1 year of active status before baseline BMI. Patients with a diagnosis or history of chronic diseases were excluded., Interventions: None., Main Outcome Measure: Recorded diagnosis of NAFLD/NASH during follow-up (Humedica International Classification of Diseases, Ninth Revision code 571.8, and read codes for NAFLD and NASH in THIN)., Results: Hazard ratios (HRs) were calculated across BMI categories using BMI of 20-22.5 kg/m(2) as the reference category, adjusting for age, sex, and smoking status. Risk of recorded NAFLD/NASH increased linearly with BMI and was approximately 5-fold higher in Humedica (HR = 4.78; 95% confidence interval, 4.17-5.47) and 9-fold higher in THIN (HR = 8.93; 7.11-11.23) at a BMI of 30-32.5 kg/m(2) rising to around 10-fold higher in Humedica (HR = 9.80; 8.49-11.32) and 14-fold higher in THIN (HR = 14.32; 11.04-18.57) in the 37.5- to 40-kg/m(2) BMI category. Risk of NAFLD/NASH was approximately 50% higher in men and approximately double in those with diabetes., Conclusions: These data quantify the consistent and strong relationships between BMI and prospectively recorded diagnoses of NAFLD/NASH and emphasize the importance of weight reduction strategies for prevention and management of NAFLD.