Bayesian two-stage modeling of longitudinal and time-to-event data with an integrated fractional Brownian motion covariance structure.

It is difficult to characterize complex variations of biological processes, often longitudinally measured using biomarkers that yield noisy data. While joint modeling with a longitudinal submodel for the biomarker measurements and a survival submodel for assessing the hazard of events can alleviate measurement error issues, the continuous longitudinal submodel often uses random intercepts and slopes to estimate both between- and within-patient heterogeneity in biomarker trajectories. To overcome longitudinal submodel challenges, we replace random slopes with scaled integrated fractional Brownian motion (IFBM). As a more generalized version of integrated Brownian motion, IFBM reasonably depicts noisily measured biological processes. From this longitudinal IFBM model, we derive novel target functions to monitor the risk of rapid disease progression as real-time predictive probabilities. Predicted biomarker values from the IFBM submodel are used as inputs in a Cox submodel to estimate event hazard. This two-stage approach to fit the submodels is performed via Bayesian posterior computation and inference. We use the proposed approach to predict dynamic lung disease progression and mortality in women with a rare disease called lymphangioleiomyomatosis who were followed in a national patient registry. We compare our approach to those using integrated Ornstein-Uhlenbeck or conventional random intercepts-and-slopes terms for the longitudinal submodel. In the comparative analysis, the IFBM model consistently demonstrated superior predictive performance.

Overcoming denominator problems in refugee settings with fragmented electronic records for health and immigration data: a prediction-based approach.

BACKGROUND: Epidemiological studies in refugee settings are often challenged by the denominator problem, i.e. lack of population at risk data. We develop an empirical approach to address this problem by assessing relationships between occupancy data in refugee centres, number of refugee patients in walk-in clinics, and diseases of the digestive system. METHODS: Individual-level patient data from a primary care surveillance system (PriCarenet) was matched with occupancy data retrieved from immigration authorities. The three relationships were analysed using regression models, considering age, sex, and type of centre. Then predictions for the respective data category not available in each of the relationships were made. Twenty-one German on-site health care facilities in state-level registration and reception centres participated in the study, covering the time period from November 2017 to July 2021. RESULTS: 445 observations ("centre-months") for patient data from electronic health records (EHR, 230 mean walk-in clinics visiting refugee patients per month and centre; standard deviation sd: 202) of a total of 47.617 refugee patients were available, 215 for occupancy data (OCC, mean occupancy of 348 residents, sd: 287), 147 for both (matched), leaving 270 observations without occupancy (EHR-unmatched) and 40 without patient data (OCC-unmatched). The incidence of diseases of the digestive system, using patients as denominators in the different sub-data sets were 9.2% (sd: 5.9) in EHR, 8.8% (sd: 5.1) when matched, 9.6% (sd: 6.4) in EHR- and 12% (sd 2.9) in OCC-unmatched. Using the available or predicted occupancy as denominator yielded average incidence estimates (per centre and month) of 4.7% (sd: 3.2) in matched data, 4.8% (sd: 3.3) in EHR- and 7.4% (sd: 2.7) in OCC-unmatched. CONCLUSIONS: By modelling the ratio between patient and occupancy numbers in refugee centres depending on sex and age, as well as on the total number of patients or occupancy, the denominator problem in health monitoring systems could be mitigated. The approach helped to estimate the missing component of the denominator, and to compare disease frequency across time and refugee centres more accurately using an empirically grounded prediction of disease frequency based on demographic and centre typology. This avoided over-estimation of disease frequency as opposed to the use of patients as denominators.

A comparison of cohorts of children with cerebral palsy from a population register and hospital admission data: A data linkage study.

BACKGROUND: Administrative health data, such as hospital admission data, are often used in research to identify children/young people with cerebral palsy (CP). OBJECTIVES: To compare sociodemographic, clinical details and mortality of children/young people identified as having CP in either a CP population registry or hospital admission data. METHODS: We identified two cohorts of children/young people (birth years 2001-2010, age at study end or death 2 months to 19 years 6 months) with a diagnosis of CP from either (i) the New South Wales (NSW)/Australian Capital Territory (ACT) CP Register or (ii) NSW hospital admission data (2001-2020). Using record linkage, these data sources were linked to each other and NSW Death, Perinatal, and Disability datasets. We determined the sensitivity and positive predictive value (PPV) of CP diagnosis in hospital admission data compared with the NSW/ACT CP Register (gold standard). We then compared the sociodemographic and clinical characteristics and mortality of the two cohorts available through record linkage using standardised mean difference (SMD). RESULTS: There were 1598 children/young people with CP in the NSW/ACT CP Register and 732-2439 children/young people with CP in hospital admission data, depending on the case definition used. The sensitivity of hospital admission data for diagnosis of CP ranged from 0.40-0.74 and PPV 0.47-0.73. Compared with children/young people with CP identified in the NSW/ACT CP Register, a greater proportion of those identified in hospital admission data (one or more admissions with G80 case definition) were older, lived in major cities, had comorbidities including epilepsy, gastrostomy use, intellectual disability and autism, and died during the study period (SMD > 0.1). CONCLUSIONS: Sociodemographic and clinical characteristics differ between cohorts of children/young people with CP identified using a CP register or hospital admission data. Those identified in hospital admission data have higher rates of comorbidities and death, suggesting some may have progressive conditions and not CP. These differences should be considered when planning and interpreting research using various data sources.

Hellenic registry of patients with home mechanical ventilation (HR-HMV): profiling sleep Apnea-Hypopnea syndrome patients across Greece.

BACKGROUND: Chronic respiratory conditions are a prominent public health issue and thus, building a patient registry might facilitate both policy decision making and improvement of clinical management processes. Hellenic Registry of patients with Home Mechanical Ventilation (HR-HMV) was initiated in 2017 and a web-based platform is used to support patient data collection. Eighteen hospital departments (including sleep labs) across Greece participate in this initiative, focusing on recording data for both children and adult patients supported by mechanical ventilation at home, including patients with Sleep Apnea-Hypopnea Syndrome (SAHS) under Positive Airway Pressure (PAP) therapy. METHODS: The HR-HMV initiative ultimately aims to provide a database for evidence-based care and policy making in this specific domain. To this end, a web information system was developed and data were manually collected by clinics and hospital departments. Legal and privacy issues (such as General Data Protection Rule compliance and technical information security measures) have been considered while designing the web application. Based on the collected data, an exploratory statistical report of SAHS patients in Greece is presented. RESULTS: Eleven out of the eighteen participating clinics and hospital departments have contributed with data by the time of the current study. More than 5000 adult and children patient records have been collected so far, the vast majority of which (i.e., 4900 patients) diagnosed with SAHS. CONCLUSION: The development and maintenance of patient registries is a valuable tool for policy decision making, observational/epidemiological research and beyond (e.g., health technology assessment procedures). However, as all data collection and processing approaches, registries are also related with potential biases. Along these lines, strengths and limitations must be considered when interpreting the collected data, and continuous validation of the collected clinical data per se should be emphasized. Especially for Greece, where the lack of national registries is eminent, we argue that HR-HMV could be a useful tool for the development and the update of related policies regarding the healthcare services for patients with home mechanical ventilation support and SAHS patients, which could be useful for related initiatives at a European level as well.

The connected patient project: moving towards a population-based primary health care research registry.

BACKGROUND: The NHS pledges to give all patients access to clinical research. In England, 32% of General Practices are research active and only 14% of patients engage in research. This project aimed to evaluate consent-for-contact and communication in primary care patients. METHODS: An explanatory mixed methods study of patients and staff within a single general practice. The study included all patients over the age of 18 years, and excluded those on the palliative care register and those unable to give informed consent. The questionnaire asked recipients to indicate their preferred contact method and data-sharing permissions with three organisations: NHS, Universities and Commercial Companies. Survey recipients and staff were invited to take part in a semi-structured interview. Interviews explored project acceptability, feasibility and reasoning behind choices made. Statistical data were triangulated with interview data. RESULTS: The target patient population was 4678, 24% (n = 1148) responded. Seven hundred and three gave permission for at least one of the organisations to contact them. Older people were more likely to respond than young people, (p < 0.001). There was a trend for more women than men to give permissions however, in the 70 years plus age group this was reversed. Short message service was the preferred method of communication (48% n = 330), but those aged 70 years and over, preferred letter (p = 0.001). Interviews suggested patients felt the project was primarily about improving communication and secondly access to research. Patients trusted the NHS and university researchers. Staff interviewees found the project was less onerous than expected. Barriers to wider rollout included workload and the fragmented nature of NHS digital systems. CONCLUSIONS: A registry of patients was established; however, the response rate of 24% needs increasing before wider adoption. Health promotion and chronic disease-based research may recruit better when based in primary health care. Older demographics would be more likely to volunteer for research. NHS and academic researchers are trusted, commercial organisations less so. The move to digitalise communication methods has the potential to marginalise older women. Findings were used to drive forward two novel developments: a consent registry (Research+Me) and a federation-wide participant identification process.

Interoperability of population-based patient registries.

Enabling full interoperability within and between population-based patient-registry domains would open up access to a rich and unique source of health data for secondary data usage. Previous attempts to tackle patient-registry interoperability have met with varying degrees of success, but a unifying solution remains elusive. The purpose of this paper is to show by practical example how a solution is attainable via the implementation of an existing framework based of the concept of federated, semantic metadata registries. One important feature motivating the use of this framework is that it can be implemented gradually and independently within each patient-registry domain. By employing linked open data principles, the framework extends the ISO/IEC 11179 standard to provide both syntactic and semantic interoperability of data elements with the means of specifying automated extraction scripts for retrieval of data from different registry content models. The examples provided address the domain of European population-based cancer registries to demonstrate the feasibility of the approach. One of the examples shows how quick gains are derivable by allowing retrieval of aggregated core data sets. The other examples show how aggregated full sets of data and record-level data might also be retrieved from each local registry. An infrastructure of patient-registry domains adhering to the principles of the framework would provide the semantic contexts and inter-linkage of data necessary for automated search and retrieval of registry data. It would thereby also lay the foundation for making registry data serviceable to artificial intelligence (AI) applications.

Minor effect of loss to follow-up on outcome interpretation in the Swedish spine register.

BACKGROUND AND PURPOSE: Loss to follow-up in observational studies may skew results and hamper study reliability. We evaluated the importance of loss to follow-up in the Swedish spine register. PATIENTS: Patients operated in the lumbar spine and scheduled for a postal questionnaire follow-up during part of 2016 were identified. Out of the 351 patients, 203 had responded. After multiple attempts, 115 of the 148 non-responders were reached; 68 returned the complete questionnaire; and 47 answered a brief questionnaire by phone. Analyses were made with the Chi-square test, analysis of covariance or logistic regression. Some analyses were adjusted. RESULTS: At baseline, the non-responders were younger than the responders (55 vs 61 years, p < 0.001) and had higher Oswestry Disability Index (ODI) (54 vs 48, p = 0.003), lower SF-36 physical component summary score (PCS) (36 vs 40, p = 0.011) and lower EQ-5D (0.17 vs 0.27, p = 0.018). Mean back pain, leg pain, ODI, EQ-5D, SF-36 mental component summary score (MCS) improved significantly in both groups (all p < 0.001). SF-36 PCS did not improve in the non-responder group (p = 0.063). Non-responders perceived less improvement in back pain (global assessment back 60% vs 72%, p = 0.002). At follow-up, there were no differences in patient-reported outcome measures between the groups (all p ≥ 0.06), with the exception of a lower SF-36 MCS among the non-responders (p = 0.015). INTERPRETATION: After surgery for lumbar spine degenerative disorders, non-responders achieve similar outcome as responders in the Swedish spine register, with the exception of a lower mental health and less perceived improvement in back pain. These slides can be retrieved under Electronic Supplementary Material.

The state of Turner syndrome science: Are we on the threshold of discovery?

Turner syndrome (TS), a genetic condition affecting roughly 1 in 2,000 females, is caused by a complete or partial loss of the second sex chromosome. This special issue of the American Journal of Medical Genetics Part C is a collection of research and clinical care reviews in TS from an international group of physician and scientist leaders who attended the 2018 "Turner Network Resource Symposium: Turner Science in the 21st Century", held in Arlington Virginia, July 15th-17th, 2018. Both this special issue and the 2018 Symposium are fueled by two rationales. First, inadequate attention has been given to health and psychosocial problems in girls and women with TS; and second, that an understanding of TS might shed light on the role of sex chromosome dosage in common conditions such as heart disease and autoimmune disease. These seminars interweave multiple themes: the fundamental partnership between participants with rare diseases and researchers, new knowledge regarding clinical care in TS, and an understanding of the "molecular phenotype" of TS-associated conditions.

The predictive validity of the Strengths and Difficulties Questionnaire for child attention-deficit/hyperactivity disorder.

We need accurate screening measures for attention-deficit/hyperactivity disorder (ADHD) to ensure that children with the disorder are referred for assessment without raising concern for children with normal behaviour. The Strengths and Difficulties Questionnaire (SDQ) provides hyperactivity-inattention (HI), conduct, emotional and peer problem subscales and impact scores that may be used for screening. The aim of the study was to investigate the predictive validity of the Danish version of the parent SDQ HI subscale at the child age of 7 years for subsequent clinically diagnosed ADHD (age 8-15 years). Participants were part of the Danish National Birth Cohort (N = 51,096), and children with ADHD were identified through the Danish National Health registries (n = 943). Receiver operating characteristic analysis showed that the screening accuracy for the HI scores was good (area under the curve = .84). With Cox multivariate regression analysis, we found that SDQ HI subscale scores ≥ 7 with impact gave a nearly 14-fold [hazard ratio (HR) = 13.59] increased risk for ADHD, while conduct and emotional problems indicated low risk (HRs of 1.62 and 1.67, respectively). For the HI subscale to be a sensitive measure for ADHD, a low cutoff (4) was needed, but gave many false screening positives (PPV = .02). Although the diagnostic accuracy of the parent version of the SDQ HI subscale for predicting ADHD was good, our results question the feasibility of screening the general child population for ADHD with only the parent SDQ HI subscale.

Incidence of new onset cancer in patients with a myocardial infarction - a nationwide cohort study.

BACKGROUND: Few studies have suggested that patients with myocardial infarction (MI) may be at increased risk of cancer, but further large register-based studies are needed to evaluate this subject. The aim of this study was to assess the incident rates of cancer and death by history of MI, and whether an MI is independently associated with cancer in a large cohort study. METHOD: All Danish residents aged 30-99 in 1996 without prior cancer or MI were included and were followed until 2012. Patients were grouped according to incident MI during follow-up. Incidence rates (IR) of cancer and death in individuals with and without MI and incidence rate ratios (IRR, using multivariable Poisson regression analyses) of cancer associated with an MI were calculated. RESULTS: Of 2,871,168 individuals, 122,275 developed an MI during follow-up, 11,375 subsequently developed cancer (9.3%, IR 19.1/1000 person-years) and 65,225 died (53.3%, IR 106.0/1000 person-years). In the reference population, 372,397 developed cancer (13.0%, IR 9.3/1000 person-years) and 753,767 died (26.3%, IR 18.2/1000 person-years). Compared to the reference population, higher IRs of cancer and death were observed in all age groups (30-54, 55-69 and 70-99 years) and time since an MI (0-1, 1-5 and 5-17 years) in the MI population. MI was associated with an increased risk of overall cancer (IRR 1.14, 95% CI 1.10-1.19) after adjusting for age, sex and calendar year, also when additionally adjusting for chronic obstructive pulmonary disease, hypertension, dyslipidemia, diabetes and socioeconomic status (IRR 1.08, 95% CI 1.03-1.13), but not after further adjustment for the first 6 months post-MI (IRR 1.00, 95% CI 0.96-1.05). CONCLUSION: Patients after an MI have increased incidence of cancer, which may be explained by mutual risk, occult cancers and increased surveillance. Focus on risk factor management to reduce cancer and MI is warranted.

[Side effects of biologic therapies in psoriasis]. / Biologikanebenwirkungen bei Psoriasis.

BACKGROUND: The introduction of biologics has revolutionized the treatment of moderate to severe plaque psoriasis. Due to the continuous expansion of biological therapies for psoriasis, it is particularly important to acknowledge efficacy and safety of the compounds not only in clinical trials but also in long-term registry-based observational studies. AIM: Typical side effects and significant risks of antipsoriatic biologic therapies considering psoriatic control groups are presented. MATERIALS AND METHODS: A selective literature search was conducted in PubMed and long-term safety studies of the psoriasis registries PsoBest, PSOLAR and BADBIR were evaluated. RESULTS AND DISCUSSION: To assess the long-term safety of biologics, the evaluation of the course of large patient cohorts in long-term registries is of particular medical importance. Newer biologic drugs seem to exhibit a better safety profile than older ones.

Natural History, Trial Readiness and Gene Discovery: Advances in Patient Registries for Neuromuscular Disease.

Inherited neuromuscular diseases (NMDs) are genetic disorders that affect the skeletal muscles or the nerves controlling muscle function. With a new generation of diagnostic options and recent advances in translational research improving the opportunities for therapy development for these rare conditions, capturing patient information in databases collecting a range of clinical and genetic data together with contact details has assumed an increasingly important role in trial planning and recruitment as well as natural history data collection. Here we provide an overview of a decade of patient registration activities in the NMD field, with a particular focus on patient registries set up with trial readiness in mind. A summary is provided of databases collecting precise genetic information focused on confirming the causative mutation and their evolution into registries that combine genetic data with additional clinical information useful for trial feasibility and recruitment. Use of these systems for a range of purposes beyond trial recruitment, including natural history assessment, care standards monitoring, genotype-phenotype correlation and disease burden evaluation is also described within the context of research networks (TREAT-NMD) and European Reference Networks (ERN-EURO-NMD). New initiatives including registries using controlled vocabularies for computational accessibility that focus on phenotypic data capture for gene discovery are analysed, and examples of the lessons learned at every stage are provided in order to allow new patient registration initiatives to benefit from the extensive experience gained.

Neonatal Lupus: What We Have Learned and Current Approaches to Care.

Neonatal lupus results from the passive transfer of autoantibodies; however, this transfer is not sufficient to cause disease. This article reviews clinical presentation with a focus on autoimmune-mediated congenital heart disease. Recent data looking for additional disease mechanisms and biomarkers as well as latest information on interventions will be reviewed. Our understanding of this rare disease is often dependent on patient participation in disease registries and biorepositories. Future participation in registries including descriptive as well as biophysical data is critical to our knowledge.

Building national patient registries in Mexico: insights from the MexOMICS Consortium.

Objective: To introduce MexOMICS, a Mexican Consortium focused on establishing electronic databases to collect, cross-reference, and share health-related and omics data on the Mexican population. Methods: Since 2019, the MexOMICS Consortium has established three electronic-based registries: the Mexican Twin Registry (TwinsMX), Mexican Lupus Registry (LupusRGMX), and the Mexican Parkinson's Research Network (MEX-PD), designed and implemented using the Research Electronic Data Capture web-based application. Participants were enrolled through voluntary participation and on-site engagement with medical specialists. We also acquired DNA samples and Magnetic Resonance Imaging scans in subsets of participants. Results: The registries have successfully enrolled a large number of participants from a variety of regions within Mexico: TwinsMX (n = 2,915), LupusRGMX (n = 1,761) and MEX-PD (n = 750). In addition to sociodemographic, psychosocial, and clinical data, MexOMICS has collected DNA samples to study the genetic biomarkers across the three registries. Cognitive function has been assessed with the Montreal Cognitive Assessment in a subset of 376 MEX-PD participants. Furthermore, a subset of 267 twins have participated in cognitive evaluations with the Creyos platform and in MRI sessions acquiring structural, functional, and spectroscopy brain imaging; comparable evaluations are planned for LupusRGMX and MEX-PD. Conclusions: The MexOMICS registries offer a valuable repository of information concerning the potential interplay of genetic and environmental factors in health conditions among the Mexican population.

Big Multiple Sclerosis Data network: an international registry research network.

BACKGROUND: The Big Multiple Sclerosis Data (BMSD) network ( https://bigmsdata.org ) was initiated in 2014 and includes the national multiple sclerosis (MS) registries of the Czech Republic, Denmark, France, Italy, and Sweden as well as the international MSBase registry. BMSD has addressed the ethical, legal, technical, and governance-related challenges for data sharing and so far, published three scientific papers on pooled datasets as proof of concept for its collaborative design. DATA COLLECTION: Although BMSD registries operate independently on different platforms, similarities in variables, definitions and data structure allow joint analysis of data. Certain coordinated modifications in how the registries collect adverse event data have been implemented after BMSD consensus decisions, showing the ability to develop together. DATA MANAGEMENT: Scientific projects can be proposed by external sponsors via the coordinating centre and each registry decides independently on participation, respecting its governance structure. Research datasets are established in a project-to-project fashion and a project-specific data model is developed, based on a unifying core data model. To overcome challenges in data sharing, BMSD has developed procedures for federated data analysis. FUTURE PERSPECTIVES: Presently, BMSD is seeking a qualification opinion from the European Medicines Agency (EMA) to conduct post-authorization safety studies (PASS) and aims to pursue a qualification opinion also for post-authorization effectiveness studies (PAES). BMSD aspires to promote the advancement of real-world evidence research in the MS field.

Houston Methodist cardiovascular learning health system (CVD-LHS) registry: Methods for development and implementation of an automated electronic medical record-based registry using an informatics framework approach.

Objectives: To investigate the potential value and feasibility of creating a listing system-wide registry of patients with at-risk and established Atherosclerotic Cardiovascular Disease (ASCVD) within a large healthcare system using automated data extraction methods to systematically identify burden, determinants, and the spectrum of at-risk patients to inform population health management. Additionally, the Houston Methodist Cardiovascular Disease Learning Health System (HM CVD-LHS) registry intends to create high-quality data-driven analytical insights to assess, track, and promote cardiovascular research and care. Methods: We conducted a retrospective multi-center, cohort analysis of adult patients who were seen in the outpatient settings of a large healthcare system between June 2016 - December 2022 to create an EMR-based registry. A common framework was developed to automatically extract clinical data from the EMR and then integrate it with the social determinants of health information retrieved from external sources. Microsoft's SQL Server Management Studio was used for creating multiple Extract-Transform-Load scripts and stored procedures for collecting, cleaning, storing, monitoring, reviewing, auto-updating, validating, and reporting the data based on the registry goals. Results: A real-time, programmatically deidentified, auto-updated EMR-based HM CVD-LHS registry was developed with ∼450 variables stored in multiple tables each containing information related to patient's demographics, encounters, diagnoses, vitals, labs, medication use, and comorbidities. Out of 1,171,768 adult individuals in the registry, 113,022 (9.6%) ASCVD patients were identified between June 2016 and December 2022 (mean age was 69.2 ± 12.2 years, with 55% Men and 15% Black individuals). Further, multi-level groupings of patients with laboratory test results and medication use have been analyzed for evaluating the outcomes of interest. Conclusions: HM CVD-LHS registry database was developed successfully providing the listing registry of patients with established ASCVD and those at risk. This approach empowers knowledge inference and provides support for efforts to move away from manual patient chart abstraction by suggesting that a common registry framework with a concurrent design of data collection tools and reporting rapidly extracting useful structured clinical data from EMRs for creating patient or specialty population registries.

StoryboardR: an R package and Shiny application designed to visualize real-world data from clinical patient registries.

Objectives: Tumor registries are a rich source of real-world data which can be used to test important hypotheses that inform clinical care. Exploratory data analysis at the level of individual subjects, when enhanced by interactive data visualizations, has the potential to provide novel insights and generate new hypothesis. Materials and Methods: We created StoryboardR: an R package and Shiny application designed to visualize real-word data from tumor registries. Results: StoryboardR facilitates the data visualization of real-word data from tumor registries captured in REDCap®. The output is an interactive timeline that allows for a visual interpretation of the relationship between potential prognostic and/or predictive biomarkers and outcomes. Conclusions: StoryboardR is freely available under the Massachusetts Institute of Technology license and can be obtained from GitHub. StoryboardR is executed in R and deployed as a Shiny application for non-R users. It produces data visualizations of patient journeys from tumor registries.

Data accuracy, consistency and completeness of the national Swiss cystic fibrosis patient registry: Lessons from an ECFSPR data quality project.

BACKGROUND: Good data quality is essential when rare disease registries are used as a data source for pharmacovigilance studies. This study investigated data quality of the Swiss cystic fibrosis (CF) registry in the frame of a European Cystic Fibrosis Society Patient Registry (ECFSPR) project aiming to implement measures to increase data reliability for registry-based research. METHODS: All 20 pediatric and adult Swiss CF centers participated in a data quality audit between 2018 and 2020, and in a re-audit in 2022. Accuracy, consistency and completeness of variables and definitions were evaluated, and missing source data and informed consents (ICs) were assessed. RESULTS: The first audit included 601 out of 997 Swiss people with CF (60.3 %). Data quality, as defined by data correctness ≥95 %, was high for most of the variables. Inconsistencies of specific variables were observed because of an incorrect application of the variable definition. The proportion of missing data was low with <5 % for almost all variables. A considerable number of missing source data occurred for CFTR variants. Availability of ICs varied largely between centers (10 centers had >5 % of missing documents). After providing feedback to the centers, availability of genetic source data and ICs improved. CONCLUSIONS: Data audits demonstrated an overall good data quality in the Swiss CF registry. Specific measures such as support of the participating sites, training of data managers and centralized data collection should be implemented in rare disease registries to optimize data quality and provide robust data for registry-based scientific research.

Outcomes of Biologic Use in Asian Compared with Non-Hispanic White Adult Psoriasis Patients from the CorEvitas Psoriasis Registry.

INTRODUCTION: Real-world data are limited comparing Asian and White patients with psoriasis using biologic therapy. This study compared the 6-month effectiveness of biologic therapy between Asian and White plaque patients with psoriasis in the CorEvitas Psoriasis Registry. METHODS: Analyses included biologic initiations and 6-month follow-up visits from self-identified Asian (n = 293) and White (n = 2314) patients in the USA/Canada (4/2015-4/2020). Outcomes included: Psoriasis Area Severity Index (PASI) 75, disease activity measures [body surface area (BSA) ≤ 1, BSA ≤ 3, PASI90, PASI100, Investigator's Global Assessment (IGA) 0/1], and patient-reported outcomes [Dermatology Life Quality Index (DLQI) 0/1, itch, fatigue, skin pain, EuroQoL visual analog scale (EQ-VAS), patient global assessment, Work Productivity Activity and Impairment (WPAI) domains]. Unadjusted regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for achievement of binary outcomes and difference in mean change in continuous outcomes (ß, 95% CI) at 6 months, followed by adjustment for age, sex, body mass index, alcohol, smoking, health insurance, education, comorbidities, scalp psoriasis morphology, psoriatic arthritis, biologic class, previous biologics, and baseline outcome value. RESULTS: Asians had lower proportions of women (32.8% versus 49.1%) and obesity (27.3% versus 54.5%), and higher proportions on Medicaid (19.9% versus 8.8%), graduated college (50.9% versus 40.1%) and never smoked (67.1% versus 44.1%). In unadjusted analyses, Asians had 52% higher odds of achieving PASI75 versus White patients (OR 1.52; 95% CI 1.15, 2.02). After adjustment, the association was attenuated (OR 1.11; 0.81, 1.52). Secondary outcomes experienced similar patterns except for DLQI: Asians had 33% lower odds of achieving DLQI 0/1 in both the unadjusted (OR 0.67; 0.50, 0.90) and adjusted (OR 0.67; 0.49, 0.92) models. CONCLUSION: Unadjusted differences in biologic therapy effectiveness between Asians compared with White patients were likely explained by differences in demographic, lifestyle, and psoriatic disease characteristics between groups. However, Asians still experienced lesser improvements in skin-related quality of life, even after adjustment.

Teamwork makes the dream work: functional collaborations between families, scientists, and healthcare providers to drive progress in the treatment of Leigh Syndrome.

BACKGROUND: Leigh syndrome, an inherited neurometabolic disorder, is estimated to be the most common pediatric manifestation of mitochondrial disease. No treatments are currently available for Leigh syndrome due to many hurdles in drug discovery efforts. Leigh syndrome causal variants span over 110 different genes and likely lead to both unique and shared biochemical alterations, often resulting in overlapping phenotypic features. The mechanisms by which pathogenic variants in mitochondrial genes alter cellular phenotype to promote disease remain poorly understood. The rarity of cases of specific causal variants creates barriers to drug discovery and adequately sized clinical trials. BODY: To address the current challenges in drug discovery and facilitate communication between researchers, healthcare providers, patients, and families, the Boston University integrative Cardiovascular Metabolism and Pathophysiology (iCAMP) Lab and Cure Mito Foundation hosted a Leigh Syndrome Symposium. This symposium brought together expert scientists and providers to highlight the current successes in drug discovery and novel models of mitochondrial disease, and to connect patients to providers and scientists to foster community and communication. CONCLUSION: In this symposium review, we describe the research presented, the hurdles ahead, and strategies to better connect the Leigh syndrome community members to advance treatments for Leigh syndrome.