Medical Record Linkage Research Articles

Generation Scotland – Linking all the records we can

ObjectivesGeneration Scotland (GS) is a family-based genetic epidemiology study. Initial recruitment between 2006-11 recruited ~24,000 adults from ~7000 families across Scotland with consent for medical record linkage and re-contact. In 2022 we began recruiting another 20,000, with consent extended to administrative records, with age range now 12+. MethodsOriginal volunteers completed a baseline questionnaire, provided biological samples and underwent clinical assessment. The samples, phenotype and genotype (including methylation) data are linked to routine NHS hospital, maternity, lab test, prescriptions, dentistry, mortality, imaging, cancer screening, GP data records, Covid-19 testing and vaccinations, and follow-up questionnaires. The new wave of recruitment is all online and can be done on a smartphone, with DNA from saliva collected by post. Teenagers aged 12-15 can join with parental consent. ResultsResearchers can find prevalent and incident disease cases and controls, to test research hypotheses on a stratified population. GS is a vanguard cohort testing emerging linkage opportunities in Scotland – including neonatal bloodspots and medical imaging reports. GS has established and validated E-HR linkage with the NHS Scotland CHI Register, overcoming technical and governance issues in the process. We contribute to major international consortia, with collaborators from institutions worldwide, both academic and commercial. ConclusionWe plan to extend the linkage process to include other administrative data from national datasets as and when approvals are obtained. New types of data can also be collected by online questionnaires. The Research Tissue Bank resources are available to academic and commercial researchers through a managed access process.

Generation Scotland Teenage Recruitment – Creating, evaluating and evolving a study sign-up process in collaboration with study participants and young people

ObjectivesGeneration Scotland (GS) is a family-based genetic epidemiology study. Initial recruitment was ~24,000 adult volunteers from across Scotland in 2006-11 with consent for medical record linkage and re-contact. In 2022 we began recruiting another 20,000, with consent extended to administrative records, with age range now 12+. MethodsPeople join the study and complete a questionnaire online, with postal saliva sample collection for DNA. Initially, the consent process required a parent/guardian to join GS, confirm their 12-15 year-old’s capacity for enduring consent and invite their child to join. After launch, parents and young people fed back that the communication and consent methods had a negative effect on the ability of young people to join GS - impacting their autonomy, as they were unable join GS independently of their parents. ResultsThe GS Team designed a new sign-up process for 12–15 year-olds that allowed the teenager to sign up first and request that their parent agree they have capacity to consent. Creating this process was done in collaboration with the new GS YPAG. This new sign-up process was launched in September 2023. We also enabled sign-up using a mobile phone number instead of an email address. ConclusionCo-design of GS recruitment with young people and parents has greatly improved the sign-up process, making GS the first UK longitudinal study where people aged 12-15 can provide enduring consent online with parental confirmation of their capacity. This provides young people with greater ownership over their ability to take part in health research.

Population-Based Incidence and Clinical Characteristics of Ocular Adnexal Tumors in Olmsted County, Minnesota

ABSTRACT Purpose To determine the incidence and clinical characteristics of ocular adnexaltumors in Olmsted County, Minnesota. Methods Retrospective population-based cohort study of all patients residing in Olmsted County, Minnesota diagnosed with any ocular tumor from January 1, 2006, to December 31, 2015. The medical records of all patients with an incident diagnosis of any ocular adnexal tumor were reviewed using the Rochester Epidemiology Project medical record linkage system for patient demographics, tumor type, and histopathologic confirmation. Incidence rates were calculated per 100,000 person-years. Poisson regression analysis was used to analyze changes in incidence over time. Results There were 717 patients diagnosed with ocular adnexal tumors during the 10-year study period, yielding an age- and sex-adjusted incidence rate of 59.7 per 100,000 (95% CI 55.4 to 64.0, p < 0.05) per year. In total, 764 tumors were diagnosed. Most tumors were eyelid lesions (N = 756, 99.0%), which were mostly benign (N = 512, 67.8%) with epidermal inclusion cysts (N = 275, 36.0%), hidrocystoma (N = 70, 9.2%), and eyelid sebaceous cysts (N = 46, 6.1%) accounting for the majority. Malignant eyelid lesions (N = 244, 31.9%) were relatively common with basal cell carcinoma (N = 184, 24.1%) and squamous cell carcinoma (N = 49, 6.4%) having the highest frequencies. Orbital tumors (N = 8, 1.0%) were infrequent. Of the orbital tumors, the most common was lacrimal gland adenoidcystic carcinoma (N = 2, 25.0%). Conclusions In a population-based setting, most ocular adnexal tumors were benign eyelid lesions. Understanding the epidemiology of ocular adnexal tumors is important to aid providers in diagnosing and facilitating appropriate referrals of potentially vision- and life-threatening malignancies.

Leading determinants of incident dementia among individuals with and without the apolipoprotein E ε4 genotype: a retrospective cohort study

BackgroundLittle is known regarding the leading risk factors for dementia/Alzheimer’s disease (AD) in individuals with and without APOE4. The identification of key risk factors for dementia/Alzheimer’s disease (AD) in individuals with and without the APOE4 gene is of significant importance in global health.MethodsOur analysis included 110,354 APOE4 carriers and 220,708 age- and sex-matched controls aged 40–73 years at baseline (between 2006–2010) from UK Biobank. Incident dementia was ascertained using hospital inpatient, or death records until January 2021. Individuals of non-European ancestry were excluded. Furthermore, individuals without medical record linkage were excluded from the analysis. Moderation analysis was tested for 134 individual factors.ResultsDuring a median follow-up of 11.9 years, 4,764 cases of incident all-cause dementia and 2065 incident AD cases were documented. Hazard ratios (95% CIs) for all-cause dementia and AD associated with APOE4 were 2.70(2.55–2.85) and 3.72(3.40–4.07), respectively. In APOE4 carriers, the leading risk factors for all-cause dementia included low self-rated overall health, low household income, high multimorbidity risk score, long-term illness, high neutrophil percentage, and high nitrogen dioxide air pollution. In non-APOE4 carriers, the leading risk factors included high multimorbidity risk score, low overall self-rated health, low household income, long-term illness, high microalbumin in urine, high neutrophil count, and low greenspace percentage. Population attributable risk for these individual risk factors combined was 65.1%, and 85.8% in APOE4 and non-APOE4 carriers, respectively. For 20 risk factors including multimorbidity risk score, unhealthy lifestyle habits, and particulate matter air pollutants, their associations with incident dementia were stronger in non-APOE4 carriers. For only 2 risk factors (mother’s history of dementia, low C-reactive protein), their associations with incident all-cause dementia were stronger in APOE4 carriers.ConclusionsOur findings provide evidence for personalized preventative approaches to dementia/AD in APOE4 and non-APOE4 carriers. A mother’s history of dementia and low levels of C-reactive protein were more important risk factors of dementia in APOE4 carriers whereas leading risk factors including unhealthy lifestyle habits, multimorbidity risk score, inflammation and immune-related markers were more predictive of dementia in non-APOE4 carriers.

Retrospective Validation of a Computerized Physiologic Equation to Predict Minute Ventilation Needs in Critically Ill Children.

Mechanical ventilation (MV) is pervasive among critically ill children. We sought to validate a computerized physiologic equation to predict minute ventilation requirements in children and test its performance against clinician actions in an in silico trial. Retrospective, electronic medical record linkage, cohort study. Quaternary PICU. Patients undergoing invasive MV, serial arterial blood gas (ABG) analysis within 1-6 hours, and pharmacologic neuromuscular blockade (NMB). ABG values were filtered to those occurring during periods of NMB. Simultaneous ABG and minute ventilation data were linked to predict serial Pa co2 and pH values using previously published physiologic equations. There were 15,121 included ABGs across 500 encounters among 484 patients, with a median (interquartile range [IQR]) of 20 (10-43) ABGs per encounter at a duration of 3.6 (2.1-4.2) hours. The median (IQR) Pa co2 prediction error was 0.00 (-3.07 to 3.00) mm Hg. In Bland-Altman analysis, the mean error was -0.10 mm Hg (95% CI, -0.21 to 0.01 mm Hg). A nested, in silico trial of ABGs meeting criteria for weaning (respiratory alkalosis) or escalation (respiratory acidosis), compared the performance of recommended ventilator changes versus clinician decisions. There were 1,499 of 15,121 ABGs (9.9%) among 278 of 644 (43.2%) encounters included in the trial. Calculated predictions were favorable to clinician actions in 1124 of 1499 ABGs (75.0%), equivalent to clinician choices in 26 of 1499 ABGs (1.7%), and worse than clinician decisions in 349 of 1499 ABGs (23.3%). Calculated recommendations were favorable to clinician decisions in sensitivity analyses limiting respiratory rate, analyzing only when clinicians made changes, excluding asthma, and excluding acute respiratory distress syndrome. A computerized equation to predict minute ventilation requirements outperformed clinicians' ventilator adjustments in 75% of ABGs from critically ill children in this retrospective analysis. Prospective validation studies are needed.

Serum Urate and Recurrent Gout

Approximately 12 million adults in the US have a history of gout, but whether serum urate levels can help predict recurrence is unclear. To assess associations of a single serum urate measurement with subsequent risk of acute gout flares and subsequent risk of hospitalizations for gout among patients in the UK with a history of gout. This retrospective study included patients with a history of gout identified from the UK between 2006 and 2010 who were followed up through Primary Care Linked Data medical record linkage until 2017 and through the Hospital Episode Statistics database until 2020. Serum urate levels at enrollment. Rate of recurrent acute gout, ascertained by hospitalization, outpatient, and prescription/procedure records, and adjusted rate ratios using negative binomial regressions. Among 3613 patients with gout (mean age, 60 years; 3104 [86%] men), 1773 gout flares occurred over a mean follow-up of 8.3 years. Of these, 1679 acute gout flares (95%) occurred in people with baseline serum urate greater than or equal to 6 mg/dL and 1731 (98%) occurred in people with baseline serum urate greater than or equal to 5 mg/dL. Rates of acute gout flares per 1000 person-years were 10.6 for participants with baseline urate levels less than 6 mg/dL, 40.1 for levels of 6.0 to 6.9 mg/dL, 82.0 for levels of 7.0 to 7.9 mg/dL, 101.3 for levels of 8.0 to 8.9 mg/dL, 125.3 for urate levels of 9.0 to 9.9 mg/dL, and 132.8 for levels greater than or equal to 10 mg/dL. Rate ratio of flares were 1.0, 3.37, 6.93, 8.67, 10.81, and 11.42, respectively, over 10 years (1.61 [1.54-1.68] per mg/dL). Rates of hospitalization per 1000 person-years during follow-up were 0.18 for those with baseline serum urate less than 6 mg/dL, 0.97 for serum urate of 6.0 to 6.9 mg/dL, 1.8 for serum urate of 7.0 to 7.9 mg/dL, 2.2 for serum urate of 8.0 to 8.9 mg/dL, 6.7 for serum urate of 9.0 to 9.9 mg/dL, and 9.7 for serum urate greater than or equal to 10 mg/dL. Rate ratios of hospitalization for gout, adjusting for age, sex, and race were 1.0, 4.70, 8.94, 10.37, 33.92, and 45.29, respectively (1.87 [1.57-2.23] per mg/dL). In this retrospective study of patients with a history of gout, serum urate levels at baseline were associated with the risk of subsequent gout flares and rates of hospitalization for recurrent gout. These findings support using a baseline serum urate level to assess risk of recurrent gout over nearly 10 years of follow-up.

Patients with normal pressure hydrocephalus have fewer enlarged perivascular spaces in the centrum semiovale compared to cognitively unimpaired individuals

IntroductionEnlarged perivascular spaces (ePVS) may be an indicator of glymphatic dysfunction. Limited studies have evaluated the role of ePVS in idiopathic normal pressure hydrocephalus (iNPH). We aimed to characterize the distribution and number of ePVS in iNPH compared to controls. MethodsThirty-eight patients with iNPH and a pre-shunt MRI were identified through clinical practice. Age- and sex-matched controls who had negative MRIs screening for intracranial metastases were identified through a medical record linkage system. The number of ePVS were counted in the basal nuclei (BN) and centrum semiovale (CS) using the Wardlaw method blinded to clinical diagnosis. Imaging features of disproportionately enlarged subarachnoid space hydrocephalus (DESH), callosal angle, Fazekas white matter hyperintensity (WMH) grade, and the presence of microbleeds and lacunes were also evaluated. ResultsBoth iNPH patients and controls had a mean age of 74 ± 7 years and were 34% female with equal distributions of hypertension, dyslipidemia, diabetes, stroke, and history of smoking. There were fewer ePVS in the CS of patients with iNPH compared to controls (12.66 vs. 20.39, p < 0.001) but the same in the BN (8.95 vs. 11.11, p = 0.08). This remained significant in models accounting for vascular risk factors (p = 0.002) and MRI features of DESH and WMH grade (p = 0.03). ConclusionsFewer centrum semiovale ePVS may be a biomarker for iNPH. This pattern may be caused by mechanical obstruction due to upward displacement of the brain leading to reduced glymphatic clearance.

Association of Anxiety and Unspecified Emotional Distress Obtained from a Medical Records Linkage System with Incident Cognitive Outcomes in a Population-Based Setting.

Studies that assess cognition prospectively and study in detail anxiety history in the participants' medical records within the context of brain aging and Alzheimer's disease are limited. To examine the associations of anxiety and unspecified emotional distress (UED) acquired throughout a person's life with prospectively collected cognitive outcomes. Mayo Clinic Study of Aging participants who were cognitively unimpaired at baseline were included. Anxiety and UED data were abstracted from the medical record using the Rochester Epidemiology Project (REP) resources and were run separately as predictors in our models. The data were analyzed using Cox proportional hazards models for the outcomes of incident mild cognitive impairment (MCI) and dementia and using linear mixed effects models for the outcomes of global and domain specific cognitive z-scores and included key covariates. The study sample (n = 1,808) had a mean (standard deviation) age of 74.5 (7.3) years and 51.4% were male. Anxiety was associated with increased risk of MCI and dementia and was associated with lower baseline cognitive z-scores and accelerated decline over time in the global, memory, and attention domains. UED was associated with faster decline in all domains except visuospatial but did not show evidence of association with incident cognitive outcomes. These results varied by medication use and timing of anxiety. Anxiety and UED both showed inverse associations with cognition. Utilization of anxiety and UED data from across the life course, as available, from the REP system adds robustness to our results.

Modeling and Statistical Analysis of Data Breach Problems in Python

The subject of the work is electronic medical record linkage threat analysis and modeling with the use of the submitted data breaches list published by the U.S. Department of Health and Human Services. Multipronged data analysis with the use of statistics utilities and data visualization has been conducted. The model forecasting the number of data breaches based on a time series mathematical model has also been built. The article reviews the tools and techniques used in data security analysis and presents practical examples of modeling and analysis that can be used in practice to improve data protection. It was shown how important it is to protect personal data, especially medical data, and what tools can be used in the educational process of data analytics for students to effect data analysis, trend assessment, and data prediction.

Abstract B056: Inflammatory dietary pattern and risk of multiple myeloma in US Black women

Abstract Background: Multiple myeloma (MM) takes a disproportionate toll on Black Americans compared to non-Hispanic whites, yet factors related to these disparities remain poorly understood. In a prior analysis of two prospective cohort studies examining diet and MM, a dietary inflammatory pattern was significantly associated with MM risk. Here, we investigate the association between dietary inflammatory index (DII) score and MM incidence in a cohort of US Black women. Methods: The Black Women’s Health Study (BWHS) is a prospective cohort study that enrolled 59,000 US self-identified Black women age 21-69 at entry in 1995. Incident cases of MM, identified among BWHS participants followed by biennial questionnaires, were confirmed via medical record review or linkage with cancer registries. We analyzed food frequency questionnaire (FFQ) data collected in 1995, excluding participants with implausible or missing FFQ data. We also excluded women diagnosed with cancer (other than non-melanoma skin cancer) prior to baseline. FFQ data were used to create a dietary inflammatory index (DII) for each person. The DII score includes total fat and cholesterol as pro-inflammatory dietary contributors, and n-3 PUFAs, selenium, and vitamin D as anti-inflammatory contributors. The DII has been previously associated with six inflammatory markers (CRP, IL-1b, IL-4, IL-6, IL-10, TNF-a). We evaluated associations of DII score quintile with MM incidence using Cox proportional hazards regression, adjusted for age, body mass index (BMI), and total energy intake (kcal/day). Results: Among 55,276 BWHS participants eligible for this analysis, we confirmed 313 incident cases of MM over 26 years of follow-up. Median age at baseline was 38 years old and median BMI was 26.6 kg/m2. The multivariable hazard ratio for women in the top quintile of DII (most pro-inflammatory diet) relative to the lowest quintile (most anti-inflammatory diet) was 0.71 (95% confidence interval: 0.43, 1.16). Conclusions: Overall, DII score was not associated with MM incidence in this cohort of US Black women. Ongoing analyses of markers of dietary inflammation and specific food groups may clarify the possible role of dietary components in MM pathogenesis. Cumulative time-varying models of DII score may also offer more robust conclusions in future analyses. Citation Format: Anisha V. Patel, Julie R. Palmer, Jessica L. Petrick, Kimberly A. Bertrand. Inflammatory dietary pattern and risk of multiple myeloma in US Black women [abstract]. In: Proceedings of the 16th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2023 Sep 29-Oct 2;Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2023;32(12 Suppl):Abstract nr B056.

Neuropsychiatric symptoms and risk of cognitive impairment: Mayo Clinic Study of Aging

AbstractBackgroundMost studies on the relationship between neuropsychiatric symptoms (NPS) and cognitive decline focus on NPS data collected over a short period of time. To better understand the association between NPS and cognitive decline, including their temporal relationship, it is important to know NPS status across a person’s life.MethodWe utilized the unique Rochester Epidemiology Project medical record linkage system that has captured medical records as far back as 1907, to abstract the psychiatric history of 1810 cognitively unimpaired participants in the population‐based Mayo Clinic Study of Aging (MCSA). Trained nurse abstractors ascertained the presence of exposure to three common NPS (anxiety, depression, and unspecified emotional distress [UED]), both before and after entry into the MCSA. We conducted Cox Proportional Hazards (PH) models using age as the time scale and adjusting for sex, education, and APOE E4 allele for each NPS in predicting mild cognitive impairment (MCI), or dementia. Additional analyses considering medication use (yes/no) and timing of NPS were also run.ResultAnxiety (Hazard Ratio [HR] = 1.47, p&lt;0.001), depression (HR = 1.36, p = 0.001), and UED (HR = 1.22, p = 0.039) were associated with a higher risk of MCI. These associations were present regardless of medication use for anxiety (With medication: HR = 1.51, p&lt;0.001; without medication: HR = 1.41, p = 0.015), and for those taking medications for depression (With medication: HR = 1.47, p&lt;0.001; without medication: 1.09, p = 0.597). Anxiety was associated with MCI regardless of timing of onset with the strongest relationship being for those with onset of anxiety before 65 that persisted into later life (HR = 1.88, p = 0.004). Depression was associated regardless of timing of onset if the depression was present in late life too. The results were similar for the outcome of dementia (Anxiety: HR = 1.62, p&lt;0.001; depression: HR = 1.31, p = 0.040; UED: HR = 1.37, p = 0.014). The associations accounting for medication use and timing of NPS were similar for the outcome of dementia too.ConclusionNPS is associated with progression to MCI and dementia. Both medication use and timing of NPS might play a role in these associations.

Generation Scotland: Linking all the records we can

ObjectivesWe started a family-based genetic epidemiology study in 2006-11 which recruited ~24,000 adult volunteers from ~7000 families across Scotland with consent for follow-up through medical record linkage and re-contact. In 2022-23 we are recruiting another 20,000, with consent extended to administrative records, with age range now 12+.&#x0D; MethodsOriginal volunteers completed a demographic, health and lifestyle questionnaire, provided biological samples, and underwent detailed clinical assessment. The samples, phenotype and genotype data form a resource for research on the genetics of conditions of public health importance. This has become a longitudinal dataset by linkage to routine NHS hospital, maternity, lab test, prescriptions, dentistry, mortality, imaging, cancer screening, GP data records, Covid-19 testing and vaccinations, as well as follow-up questionnaires. The new wave of recruitment is all online and can be done on a smartphone, with DNA from saliva collected by post. Teenagers aged 12-15 can join with parental consent.&#x0D; Results GWAS has been done on quantitative traits and biomarkers, with DNA methylation data and proteomics available for most of the cohort. Our “CovidLife” surveys collected data on effects of the pandemic.&#x0D; Researchers can find prevalent and incident disease cases and controls, to test research hypotheses on a stratified population. They can also do targeted recruitment of participants to new studies, including recall by genotype. We have established and validated E-HR linkage with the NHS Scotland CHI Register,,overcoming technical and governance issues in the process. We contribute to major international consortia, with collaborators from institutions worldwide, both academic and commercial. Recruits are asked to give consent to linkage to other administrative data, and reuse of samples from routine NHS tests for medical research.&#x0D; Conclusion We plan to extend the linkage process to include other administrative data from national datasets as and when approvals are obtained. New types of data can also be collected by online questionnaires. The Research Tissue Bank resources are available to academic and commercial researchers through a managed access process.

The United KingdomEating Disorders Genetics Initiative.

The United Kingdom Eating Disorders Genetics Initiative (EDGI UK), part of the National Institute for Health and Care Research (NIHR) Mental Health BioResource, aims to deepen our understanding of the environmental and genetic etiology of eating disorders. EDGI UK launched in February 2020 and is partnered with the UK eating disorders charity, Beat. Multiple EDGI branches exist worldwide. This article serves the dual function of providing an in-depth description of our study protocol and of describing our initial sample including demographics, diagnoses, and physical and psychiatric comorbidities. EDGI UK recruits via media and clinical services. Anyone living in England, at least 16 years old, with a lifetime probable or clinical eating disorder is eligible to sign up online: edgiuk.org. Participants complete online questionnaires, donate a saliva sample for genetic analysis, and consent to medical record linkage and recontact for future studies. As of September 2022, EDGI UK recruited 7435 survey participants: 98% female, 93.1% white, 97.8% cisgender, 65.9% heterosexual, and 52.1% have a university degree. Over half (57.8%) of these participants have returned their saliva DNA kit. The most common diagnoses are anorexia nervosa (48.3%), purging disorder (37.8%), bulimia nervosa (37.5%), binge-eating disorder (15.8%), and atypical anorexia nervosa (7.8%). EDGI UK is the largest UK eating disorders study and efforts to increase its diversity are underway. It offers a unique opportunity to accelerate eating disorder research. Researchers and participants with lived experience can collaborate on projects with unparalleled sample size. Eating disorders are debilitating and costly for society but are under-researched due to underfunding. EDGI UK is one of the largest eating disorder studies worldwide with ongoing recruitment. The collected data constitute a resource for secondary analysis. We will combine data from all international EDGI branches and the NIHR BioResource to facilitate research that improves our understanding of eating disorders and their comorbidities.

Choroidal Nevus Features Associated with Subspecialty Referral

To identify choroidal nevus features associated with referral to a retina or ocular oncology subspecialist. Population-based retrospective cohort study. Patients diagnosed with choroidal nevus. Population-based retrospective cohort study of residents of Olmsted County, Minnesota, with an incident diagnosis of choroidal nevus from January 1, 2006, to December 31, 2015 using the Rochester Epidemiology Project, a medical record linkage system. Tumor features and patient demographics associated with referral to a retina or ocular oncology subspecialist were assessed. Wilcoxon rank sum test, chi-square test, and Fisher exact test were used for statistical analysis. Tumor features and patient demographics associated with referral to subspecialty care. There were 826 incident diagnoses of choroidal nevus, of which 88 cases (11%) were referred, with highest level of referral being retina in 29 cases (33%) and ocular oncology in 59 cases (67%). None of the analyzed demographic features were associated with choroidal nevus referral to subspecialty care. Tumor features associated with referral (vs. not referred) included greater mean basal diameter (4.6 mm vs. 2.4 mm, P<0.001), greater mean tumor thickness (0.7 mm vs. 0.1 mm, P < 0.001), greater distance to optic disc (6.9 mm vs. 3.4 mm, P= 0.02), halo around nevus (5.7% vs. 0.4%, P < 0.001), and drusen on OCT (51% vs. 25%, P=0.002). Presence of orange pigment (8% vs. 0%, P= 0.14), subretinal fluid (9% vs. 2.5%, P= 0.09), and low internal reflectivity on A-scan (7.7% vs. 0%, P= 1.00) were not found more frequently in the subspecialty referral group. Greater basal diameter and mean tumor thickness of choroidal nevus were associated with referral to retina or ocular oncology. However, several features associated with increased risk of malignant transformation were not associated with subspecialty referral. These findings highlight the importance of educating eye care providers about high-risk tumor features associated with choroidal nevus transformation to melanoma. In the primary eye care setting where not all multimodal imaging may be available, we encourage color photography and OCT with referral for any features of basal diameter > 5 mm, presence of subretinal fluid, or thickness too large for capture by enhanced-depth imaging OCT. The authors have no proprietary or commercial interest in any materials discussed in this article.

Tumefactive Demyelination in MOG Ab-Associated Disease, Multiple Sclerosis, and AQP-4-IgG-Positive Neuromyelitis Optica Spectrum Disorder.

Studies on tumefactive brain lesions in myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG)-associated disease (MOGAD) are lacking. We sought to characterize the frequency clinical, laboratory, and MRI features of these lesions in MOGAD and compare them with those in multiple sclerosis (MS) and aquaporin-4-IgG-positive neuromyelitis optica spectrum disorder (AQP4+NMOSD). We retrospectively searched 194 patients with MOGAD and 359 patients with AQP4+NMOSD with clinical/MRI details available from the Mayo Clinic databases and included those with ≥1 tumefactive brain lesion (maximum transverse diameter ≥2 cm) on MRI. Patients with tumefactive MS were identified using the Mayo Clinic medical record linkage system. Binary multivariable stepwise logistic regression identified independent predictors of MOGAD diagnosis; Cox proportional regression models were used to assess the risk of relapsing disease and gait aid in patients with tumefactive MOGAD vs those with nontumefactive MOGAD. We included 108 patients with tumefactive demyelination (MOGAD = 43; AQP4+NMOSD = 16; and MS = 49). Tumefactive lesions were more frequent among those with MOGAD (43/194 [22%]) than among those with AQP4+NMOSD (16/359 [5%], p < 0.001). Risk of relapse and need for gait aid were similar in tumefactive and nontumefactive MOGAD. Clinical features more frequent in MOGAD than in MS included headache (18/43 [42%] vs 10/49 [20%]; p = 0.03) and somnolence (12/43 [28%] vs 2/49 [4%]; p = 0.003), the latter also more frequent than in AQP4+NMOSD (0/16 [0%]; p = 0.02). The presence of peripheral T2-hypointense rim, T1-hypointensity, diffusion restriction (particularly an arc pattern), ring enhancement, and Baló-like or cystic appearance favored MS over MOGAD (p ≤ 0.001). MRI features were broadly similar in MOGAD and AQP4+NMOSD, except for more frequent diffusion restriction in AQP4+NMOSD (10/15 [67%]) than in MOGAD (11/42 [26%], p = 0.005). CSF analysis revealed less frequent positive oligoclonal bands in MOGAD (2/37 [5%]) than in MS (30/43 [70%], p < 0.001) and higher median white cell count in MOGAD than in MS (33 vs 6 cells/μL, p < 0.001). At baseline, independent predictors of MOGAD diagnosis were the presence of somnolence/headache, absence of T2-hypointense rim, lack of T1-hypointensity, and no diffusion restriction (Nagelkerke R 2 = 0.67). Tumefactive lesion resolution was more common in MOGAD than in MS or AQP4+NMOSD and improved model performance. Tumefactive lesions are frequent in MOGAD but not associated with a worse prognosis. The clinical, MRI, and CSF attributes of tumefactive MOGAD differ from those of tumefactive MS and are more similar to those of tumefactive AQP4+NMOSD with the exception of lesion resolution, which favors MOGAD.

Clinical course of non-alcoholic fatty liver disease and the implications for clinical trial design.

The predicted risk and timeline to progression to liver-related outcomes in the population with NAFLD are not well-characterized. We aimed to examine the risk and time to progression to cirrhosis, hepatic decompensation and death in a contemporary population over a long follow-up period, to obtain information to guide endpoint selection and sample size calculations for clinical trials on NAFLD-related cirrhosis. This is a retrospective study of prospectively collected data in a medical record linkage system, including all adults diagnosed with NAFLD between 1996-2016 by clinical, biochemical and radiological criteria in Olmsted County, Minnesota and followed until 2019. Liver-related outcomes and death were ascertained and validated by individual medical record review. Time and risk of progression from NAFLD to cirrhosis to decompensation and death were assessed using multistate modeling. A total of 5,123 individuals with NAFLD (median age 52 years, 53% women) were followed for a median of 6.4 (range 1-23) years. The risk of progression was as follows: from NAFLD to cirrhosis: 3% in 15 years; compensated cirrhosis to first decompensation: 33% in 4 years (8%/year); first decompensation to ≥2 decompensations: 48% in 2 years. Albumin, bilirubin, non-bleeding esophageal varices and diabetes were independent predictors of decompensation. Among the 575 deaths, 6% were liver related. Therapeutic trials in compensated cirrhosis would require enrolment of a minimum of 2,886 individuals followed for >2 years to detect at least a 15% relative decrease in liver-related endpoints. In this population-based cohort with 23 years of longitudinal follow-up, NAFLD was slowly progressive, with liver-related outcomes affecting only a small proportion of people. Large sample sizes and long follow-up are required to detect reductions in liver-related endpoints in clinical trials. For patients with compensated non-alcoholic steatohepatitis-related cirrhosis, the time spent in this state and the risk of progression to decompensation are not well-known in the population. We examined the clinical course of a large population-based cohort over 23 years of follow-up. We identified that adults with compensated cirrhosis spend a mean time of 4 years in this state and have a 10% per year risk of progression to decompensation or death. The risk of further progression is 3-fold higher in adults with cirrhosis and one decompensating event. These results are reflective of placebo arm risks in drug clinical trials and are essential in the estimation of adequate sample sizes.

Does Physical Activity Mitigate The Risk Of Frailty-related Bone Fractures Among Cancer Survivors?

Cancer and associated treatments may predispose survivors to a higher risk of frailty-related bone fractures. Whether physical activity offsets some of the excess risk is poorly understood. Prior studies lacked detailed information on physical activity (because it is not well captured by administrative data sources), had small sample sizes, and were limited to certain cancer types. PURPOSE: Investigate associations between cancer history and subsequent risk of frailty-related fractures, and to explore modification by moderate-vigorous intensity aerobic physical activity (MVPA) and weight training. METHODS: Participants from the Cancer Prevention Study-II (CPS-II) were linked to Medicare claims data for years 1999-2017. Cancer history was confirmed via medical record or cancer registry linkage starting at CPS-II enrollment (1992) and modeled as a time-dependent variable in three categories: 1) cancer survivor 1-5 years post-diagnosis (short-term), 2) cancer survivor ≥5 years post-diagnosis (longer-term), and 3) no cancer history. The first year of diagnosis was excluded to reduce the effect of treatment. Total frailty-related (pelvic, radial, vertebral) and site-specific fractures were identified in Medicare claims data using established algorithms. Multivariable Cox proportional hazards regression was used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for risk of fractures overall and stratified by MVPA and weight training. RESULTS: Over the course of follow-up, 14,196 frailty-related fractures were identified among 101,543 participants (including 14,159 cancer survivors). Compared to no cancer history, both short- (HR=1.28, CI: 1.18-1.38) and longer-term (HR=1.08, CI: 1.00-1.16) cancer survivors were at higher risk of total frailty-related fractures. Short-term survivors were also at higher risk of pelvic (1.34, 1.18-1.53) and radial (1.33, 1.19-1.48), but not vertebral fractures. Meeting MVPA guidelines (0.87, 0.78-0.97) and weight training (0.85, 0.74-0.99) lowered risk of fractures among longer-term survivors, but not short-term survivors (0.94, 0.81-1.09 MVPA and 0.95, 0.78-1.17 weight training). CONCLUSION: Cancer survivors are at a higher risk of frailty-related fractures, but MVPA and weight training may reduce some of the excess risk.

Revisiting the Quality of the Scottish Record Linkage System.

ObjectivesTo evaluate the quality of linkage carried out by operators in the Trusted Third Parties (TTPs) in Public Health Scotland (PHS) and National Records of Scotland (NRS). To compare results with a PHS automated production system. To produce individual reports to feedback results to operators, informing areas for improvement. ApproachA test dataset (n=274,479) containing names, dates of birth, sex and postcode, was derived from hospital episodes and additional synthetic records added. For a proportion of records, some variables were perturbed. The true reference index number was retained to compare against the indexes returned by operators from matching to the population spine. A run of the Medical Record Linkage (MRL) system (used to routinely link the centrally held hospitalisations, cancer and death registrations over the last 25 years) was executed without clerical review, to provide a benchmark for the TTPs. Recall, precision and F-measures were calculated to compare results. ResultsThere were 5 reports produced, including the MRL run. NRS contributed a single run, and PHS-TTP offered 3. Quality overall was excellent, with some variation dependent on operator, methods, and spine used. The MRL run was ranked 3rd overall for F-measure, with overall precision of 99.69% and 97.36% recall. Where data had been unperturbed precision was 99.92% with 99.90% recall. The best ranked run was carried out by a member of PHS TTP, with 99.72% precision (99.93% unperturbed) and 98.77% recall (99.94% unperturbed). NRS results showed precision of 99.56% (99.91% unperturbed) and 96.71% recall (99.80% unperturbed). Individual reports were produced and tailored to highlight the types of perturbations where each operator performed strongly or otherwise, encouraging operators to learn and adapt processes in future. ConclusionData Linkage in Scotland has evolved over 5 decades, more recently with the introduction of TTPs as key support services for research projects. However, little evaluation of the quality of linkage has been conducted. The results demonstrated by this exercise provide re-assurance to researchers that linkage quality remains high

Reconstruction of pseudonymized patient-trajectories in Austria's stroke cohort using medical record-linkage of in-patient routine documentation to establish a nation-wide acute stroke cohort of 102,107 pseudonymized patients between 2015 and 2019.

Administrative health data are increasingly used for disease surveillance, quality assurance and research purposes. In Austria, reporting of a standardized dataset is mandatory for each patient. Routine documentation includes administrative and medical data, including admission and discharge characteristics, disease-diagnosis using ICD-10, medical procedure codes, and coding of involved hospital departments. Since 2015, a three-step pseudonymization on these data is provided including a pseudonym using secure hash algorithm 256, a non-recalculable record-ID, and age-groups of 5 years, allowing the reconstruction of individual patient-trajectories. We included persons aged ⩾20 years with an in-patient treatment in Austrian hospitals for acute stroke or transient ischemic attack (TIA) between 01.01.2015 and 31.12.2019 using medical record-linkage. This totals 102,107 patients (49.3% women) with 107,055 treatment episodes. An ischemic stroke (IS) occurred in 60.9% (n = 65,133), 27.1% (n = 29,019) had a TIA, 3.3% (n = 3488) a subarachnoid hemorrhage, and 8.8% (n = 9415) an intracerebral hemorrhage (ICH). The study period covers 35.2 million person-years at risk, with a hospitalization rate for acute stroke of 221.8 per 100,000 person-years (95% CI 220.2-223.3), and 185.1 per 100,000 person-years (95% CI 183.7-186.5) for IS. Unscheduled re-admissions within 1 year occurred in 29.2% (95% CI 28.8-29.7) after IS, and 41.7% (95% CI 40.0-43.3) after ICH. Recurrent stroke occurred in 5.3% (95% CI 5.1-5.5) after IS, and 5.6% (95% CI 4.9-6.4) after ICH. We present herein the details of a novel methodology to establish a nation-wide unselected Austrian stroke cohort, and to reconstruct pseudonymized individual longitudinal patient-trajectories on a national level. This approach shows potential applications in epidemiological research, quality assessment and outcome measurement. This novel approach opens new research fields, facilitates international comparison, and is needed for national benchmarking to assess the achievement of goals according to the Stroke Action Plan for Europe and augment the quality of Austria's integrated stroke care.

Hospitalization rates, stroke unit care, and recurrence rates in Austria's stroke cohort Epidemiologic analysis of 102,107 patients in a nation-wide acute stroke cohort between 2015 and 2019.

Continuous analysis of key epidemiologic data is irremissible to adapt health-care systems to trends in stroke epidemiology. We present data from 2015 to 2019 on quality indicators of stroke care, including rates on hospitalization, stroke unit care and recurrence rates using medical record-linkage of in-patient routine documentation. We included stroke/TIA patients admitted to Austrian hospitals between 2015 and 2019 aged ⩾20 years using medical record-linkage. In our cohort of 102,107 patients with 107,055 treatment episodes, we could show a significant decrease in 1-year cumulative age-adjusted hospitalization rates per 100,000 in TIA (86.3 [95% CI 84.1-88.5] vs 75.4 [95% CI 73.4-77.4], RR 0.87 [95% CI 0.85-0.90]), ischemic stroke (187.3 [95% CI 184.0-190.5] vs 173.4 [95% CI 170.4-176.5], RR 0.93 [95% CI 0.91-0.94]), and intracerebral hemorrhage (28.5 [95% CI 27.3-29.8] vs 22.8 [95% CI 21.7-23.9], RR 0.80 [95% CI 0.76-0.84]). In ischemic stroke the rate of stroke unit care increased significantly (55.7% vs 69.3%; RR 1.14 [95% CI 1.12-1.17]), and acute 1-year recurrences decreased significantly. We found a decline of the annual age-adjusted cumulative hospitalization rates in stroke/TIA, a higher age of disease manifestation and less severe strokes, which is probably attributable to improved primary and secondary prevention in Austria. The proportion of patients treated at stroke units increased significantly, however a geographical and age-dependency is still evident. Age-adjusted hospitalization rates of stroke/TIA patients decreased, and stroke unit care is increasing but the goal of the Stroke Action Plan for Europe is yet to be reached.