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Aim: Validity of Algorithms in Large Databases: Infectious Diseases, Rheumatoid Arthritis, and Tumor Evaluation in Japan (VALIDATE‐J) study examined algorithms for identifying rheumatoid arthritis (RA) in Japanese claims data. Methods: VALIDATE‐J was a multicenter, cross‐sectional retrospective study. Disease‐identifying algorithms were used to detect RA diagnosed between January 2012 and December 2016 using claims data from two Japanese hospitals. An RA diagnosis was confirmed using one of four gold standard definitions. Positive predictive values (PPVs) were calculated for prevalent (regardless of baseline RA‐free period) and incident (preceded by a 12‐month RA‐free period) cases. Results: Of patients identified using claims‐based algorithms, a random sample of 389 prevalent and 134 incident cases of RA were included. Cases identified by an RA diagnosis, no diagnosis of psoriasis, and treatment with any disease‐modifying antirheumatic drugs (DMARDs) resulted in the highest PPVs versus other claims‐based treatment categories (29.0%–88.3% [prevalent] and 41.0%–78.2% [incident]); cases identified by an RA diagnosis, no diagnosis of psoriasis, and glucocorticoid‐only treatment had the lowest PPVs. Across claims‐based algorithms, PPVs were highest when a physician diagnosis or decision by adjudicators (confirmed and probable cases) was used as the gold standard and were lowest when American College of Rheumatology/European Alliance of Associations for Rheumatology 2010 criteria were applied. PPVs of claims‐based algorithms for RA in patients aged ≥66 years were slightly higher versus a USA Medicare population (maximum PPVs of 95.0% and 88.9%, respectively). Conclusion: VALIDATE‐J demonstrated high PPVs for most claims‐based algorithms for diagnosis of prevalent and incident RA using Japanese claims data. These findings will help inform appropriate RA definitions for future claims database research in Japan. [ABSTRACT FROM AUTHOR]

Purpose: To describe and categorize detailed components of databases in the Neurological and Mental Health Global Epidemiology Network (NeuroGEN).Methods: An online 132-item questionnaire was sent to key researchers and data custodians of NeuroGEN in North America, Europe, Asia and Oceania. From the responses, we assessed data characteristics including population coverage, data follow-up, clinical information, validity of diagnoses, medication use and data latency. We also evaluated the possibility of conversion into a common data model (CDM) to implement a federated network approach. Moreover, we used radar charts to visualize the data capacity assessments, based on different perspectives.Results: The results indicated that the 15 databases covered approximately 320 million individuals, included in 7 nationwide claims databases from Australia, Finland, South Korea, Taiwan and the US, 6 population-based electronic health record databases from Hong Kong, Scotland, Taiwan, the Netherlands and the UK, and 2 biomedical databases from Taiwan and the UK.Conclusion: The 15 databases showed good potential for a federated network approach using a common data model. Our study provided publicly accessible information on these databases for those seeking to employ real-world data to facilitate current assessment and future development of treatments for neurological and mental disorders. [ABSTRACT FROM AUTHOR]

Mice deficient in the Polycomb repressor Bmi1 develop numerous abnormalities including a severe defect in stem cell self-renewal, alterations in thymocyte maturation and a shortened lifespan. Previous work has implicated de-repression of the Ink4a/Arf (also known as Cdkn2a) locus as mediating many of the aspects of the [Bmi1.sup.-/-] phenotype. Here we demonstrate that cells derived from [Bmi1.sup.-/-] mice also have impaired mitochondrial function, a marked increase in the intracellular levels of reactive oxygen species and subsequent engagement of the DNA damage response pathway. Furthermore, many of the deficiencies normally observed in [Bmi1.sup.-/-] mice improve after either pharmacological treatment with the antioxidant N-acetylcysteine or genetic disruption of the DNA damage response pathway by Chk2 (also known as Chek2) deletion. These results demonstrate that Bmi1 has an unexpected role in maintaining mitochondrial function and redox homeostasis and indicate that the Polycomb family of proteins can coordinately regulate cellular metabolism with stem and progenitor cell function., Bmi1 is a member of the Polycomb family of transcriptional repressors that mediate gene silencing by regulating chromatin structure and is essential for the maintenance and self-renewal of both haematopoietic [...]

Background and Aim: The prevalence of ulcerative colitis (UC) is increasing in Japan. Validated claims‐based definitions are required to investigate the epidemiology of UC and its treatment and disease course in clinical practice. This study aimed to develop a claims‐based algorithm for UC in Japan. Methods: A committee of epidemiologists, gastroenterologists, and internal medicine physicians developed a claims‐based definition for UC, based on diagnostic codes and claims for UC treatments, procedures (cytapheresis), or surgery (postoperative claims). Claims data and medical records for a random sample of 200 cases per site at two large tertiary care academic centers in Japan were used to calculate the positive predictive value (PPV) of the algorithm for three gold standards of diagnosis, defined as physician diagnosis in the medical records, adjudicated cases, or registration in the Japanese Intractable Disease Registry (IDR). Results: Overall, 1139 claims‐defined UC cases were identified. Among 393 randomly sampled cases (mean age 44; 48% female), 94% had received ≥ 1 systemic treatment (immunosuppressants, tumor necrosis factor inhibitors, corticosteroids, or antidiarrheals), 7% had cytapheresis, and 7% had postoperative claims. When physician diagnosis was used as a gold standard, PPV was 90.6% (95% confidence interval [CI]: 87.7–93.5). PPV with expert adjudication was also 90.6% (95% CI: 87.7–93.5). PPVs with enrollment in the IDR as gold standard were lower at 41.5% (95% CI: 36.6–46.3) due to incomplete case registration. Conclusions: The claims‐based algorithm developed for use in Japan is likely to identify UC cases with high PPV for clinical studies using administrative claims databases. [ABSTRACT FROM AUTHOR]

Purpose: Real‐world data from large administrative claims databases in Japan have recently become available, but limited evidence exists to support their validity. VALIDATE‐J validated claims‐based algorithms for selected cancers in Japan. Methods: VALIDATE‐J was a multicenter, cross‐sectional, retrospective study. Disease‐identifying algorithms were used to identify cancers diagnosed between January or March 2012 and December 2016 using claims data from two hospitals in Japan. Positive predictive values (PPVs), specificity, and sensitivity were calculated for prevalent (regardless of baseline cancer‐free period) and incident (12‐month cancer‐free period; with claims and registry periods in the same month) cases, using hospital cancer registry data as gold standard. Results: 22 108 cancers were identified in the hospital claims databases. PPVs (number of registry cases) for prevalent/incident cases were: any malignancy 79.0% (25 934)/73.1% (18 119); colorectal 84.4% (3519)/65.6% (2340); gastric 87.4% (3534)/76.8% (2279); lung 88.1% (2066)/79.9% (1636); breast 86.4% (4959)/59.9% (3185); pancreatic 87.1% (582)/80.4% (508); melanoma 48.7% (46)/42.9% (36); and lymphoma 83.6% (1457)/77.8% (1035). Specificity ranged from 98.3% to 100% (prevalent)/99.5% to 100% (incident); sensitivity ranged from 39.1% to 67.6% (prevalent)/12.5% to 31.4% (incident). PPVs of claims‐based algorithms for several cancers in patients ≥66 years of age were slightly higher than those in a US Medicare population. Conclusions: VALIDATE‐J demonstrated high specificity and modest‐to‐moderate sensitivity for claims‐based algorithms of most malignancies using Japanese claims data. Use of claims‐based algorithms will enable identification of patient populations from claims databases, while avoiding direct patient identification. Further research is needed to confirm the generalizability of our results and applicability to specific subgroups of patient populations. [ABSTRACT FROM AUTHOR]

WHIM is an acronym for a rare immunodeficiency syndrome (OMIM #193670) caused by autosomal dominant mutations truncating the C-terminus of the chemokine receptor CXC chemokine receptor 4 (CXCR4). WHIM mutations may potentiate CXCR4 signalling, suggesting that the United States Food and Drug Administration (FDA)-approved CXCR4 antagonist AnorMED3100 (AMD3100) (also known as Plerixafor) may be beneficial in WHIM syndrome. We have tested this at the preclinical level by comparing Chinese hamster ovary (CHO) and K562 cell lines matched for expression of recombinant wild-type CXCR4 (CXCR4WT) and the most common WHIM variant of CXCR4 (CXCR4R334X), as well as leucocytes from a WHIM patient with the CXCR4R334X mutation versus healthy controls. We found that CXCR4R334X mediated modestly increased signalling (∼2-fold) in all functional assays tested, but strongly resisted ligand-dependent down-regulation. AMD3100 was equipotent and equieffective as an antagonist at CXCR4R334X and CXCR4WT. Together, our data provide further evidence that CXCR4R334X is a gain-of-function mutation, and support clinical evaluation of AMD3100 as mechanism-based treatment in patients with WHIM syndrome. [ABSTRACT FROM AUTHOR]

Background: The Cystic Fibrosis Foundation Patient Registry (CFFPR) provides valuable clinical and demographic data but includes limited information on health services and medications provided outside of CF Care Centers. Linking CFFPR to claims databases such as national Medicaid data could address these data gaps., Methods: Linkage algorithms based on state of residence, gender, and date of birth were utilized to match individuals with CF diagnostic codes in national Medicaid databases (2016) to individuals in the CFFPR (2015-2016). Subsets of individuals with partial social security numbers or residing in the state of North Carolina were utilized to validate the accuracy of linkages and perform exploratory analyses on care utilization and costs., Results: Of the 32,152 individuals in CFFPR, 10,616 were uniquely linked to national Medicaid databases. The 372 linked individuals within the NC extract had 8.0 ± 7.6 visits to outpatient providers, substantially higher than the 4.2 ± 2.4 CF Care Center outpatient visits documented within CFFPR. Similarly, linked individuals had 2.1 ± 1.7 oral antibiotic prescriptions within CMS pharmacy databases versus 0.5 ± 1.9 oral antibiotic prescriptions in CFFPR. Total pharmacy costs for the linked individuals in NC were $16.4 million, with pancrealipase (19 %), dornase alfa (24 %), and CFTR modulators (29 %) the largest expenditures. Total non-pharmacy costs were $7.5 million, with inpatient hospitalization representing 53 % of costs., Conclusion: Linkage of data from Medicaid and CFFPR can produce valid comprehensive data on low-income people with CF and provide opportunities to examine utilization/adherence or comparative effectiveness and safety of medications as well as conduct economic analyses in the low-income CF population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.)

Wearable sensors, such as inertial measurement units (IMU), provide the ability to quantify gait parameters outside of traditional gait laboratory settings. Walking speed has been shown to be associated with morbidity and mortality. Therefore, the ability of a clinician to easily and inexpensively measure gait speed within their clinic or patients' home setting can improve patient management and care. This study highlights multiple methods used to estimate patient walking speeds based only on IMU data and minimal anthropometric data, and identifies the algorithm appearing to be the most robust; one relying on identifying swing phases of gait first.Clinical relevance- Providing a clinician with a simple, inexpensive and reliable protocol for measuring patients' gait speed and other parameters could offer prevention and individualized care.