Clinical Registry Data Research Articles

Trimetazidine reduces stroke risk in ischemic atrial fibrillation: a territory-wide, propensity-matched study

Abstract Introduction Trimetazidine ameliorates myocardial ischemia via potentiating glucose oxidation. Whether such metabolic reprogramming protects against stroke risk in atrial fibrillation (AF) with ischemic heart disease (IHD) was unknown. Purpose To investigate the therapeutic impact of trimetazidine dihydrochloride on ischemic stroke in AF associated with IHD. Methods We collected data from a territory-wide clinical data registry (January 1999 to December 2020) with a coverage of 7.5 million population. 200,563 patients with IHD were identified. Amongst them, 13,092 (6.5%) had baseline AF (mean [SD] age: 79.7 [10.3] years, 44.8% female), and were identified as trimetazidine users (n=1,488) versus non-users (long-acting nitrates as control, n=11,604). Propensity matching at 1:1 was performed. Multivariable Cox regression was used to derive hazard ratios (HRs) for new-onset ischemic stroke. Result Over mean follow-up over 53.5 +/- 50.4 months, trimetazidine use was associated with a lower incidence of ischemic stroke (3.4% vs 7.6%, P<.001). Kaplan-Meier analyses showed trimetazidine use was associated with increased stroke-free survival period (Mean survival: 227.9 [4.9] versus 217.5 [3.6] months, Chi-square=39.0 P<.001). After adjusting for confounding factors, trimetazidine use remained an independent predictor of reduced ischemic stroke risk (adjusted HRs, 0.54, 95% CI, 0.37-0.78, P<.001). Conclusion Trimetazidine may reduce the risk of ischemic stroke in ischemic AF. These findings will need to be confirmed by randomized controlled trials.

Digital health technology to support patient-centered shared decision making at point of care for juvenile idiopathic arthritis

Despite availability of multiple FDA approved therapies, many children with juvenile idiopathic arthritis (JIA) suffer pain and disability due to uncontrolled disease. The term JIA includes a heterogeneous set of conditions unified by chronic inflammatory arthritis, collectively affecting 1:1,000 children. When reviewing treatment options with families the rheumatologist currently refers to the experience of the average patient in relatively small controlled clinical trials, to consensus-based treatment plans, or increasingly the choice is dictated by the formulary restrictions of insurance payers. The current paradigm for treatment selection does not incorporate real-world evidence of treatment effectiveness centered to the individual patients with whom decisions are to be made. Treatment decisions based on the evidence of the average patient are not optimized to reflect the unique clinical characteristics of an individual with JIA and their disease course, nor does it account for heterogeneous treatment effects. To guide treatment choices centered around each patient, we describe a novel concept of utilizing digital health technology to bring patient-centered information into shared decision-making discussions based on comparative effectiveness analysis of electronic health record or observational clinical registry data of patients with similar characteristics. The envisioned digital tool will organize and present data relevant to the individual patient and enable evidence-based individualized treatment decision making when used in a collaborative manner with the patient family and rheumatologist. Capabilities in digital health technology, data capturing, and analytical methodologies are ripe for this endeavor. This brings the concept of a learning health system directly to the point of care.

Patient-reported outcomes in cancer survivorship: insights from two decades of population-based PROFILES registry research.

When the field of cancer survivorship research was in its infancy, the PROFILES registry was set up in 2004 to monitor patient-reported outcomes (PROs) in survivors and a normative population. This scoping review aims to summarize lessons learned from developing a population-based PRO registry, focusing on study methodologies, data collection shifts, data utilization, multidisciplinary collaboration, societal impact, and data sharing. A systematic computerized literature search through PubMed was performed to collect all publications using data from the PROFILES registry between January 1, 2004, and December 31, 2023. The PROFILES registry's research today encompassed 249 papers from 35 studies. Key insights include the importance of multi-hospital collaboration, which enhances participant inclusion and result generalizability. Optimizing response rates and patient inclusion is achieved through proactive data collection methods such as inclusion by health care professionals, and using both web-based and paper questionnaires. Longitudinal studies, despite their intensive data collection efforts, provide critical insights into the consequences of cancer and its treatment on patient-reported outcomes (PROs) from diagnosis through survivorship. Combining PRO data with comprehensive clinical registry data ensures reliable datasets, crucial for drawing meaningful conclusions. The shift towards multidisciplinary collaboration, open-access publishing, and data sharing all contribute to accessible and impactful research. This review highlights key insights from the PROFILES registry, emphasizing multi-hospital collaboration, proactive data collection, and the integration of PROs with clinical data. These lessons can guide future research on cancer survivorship, improving methodologies to enhance survivorship care and quality of life through multidisciplinary collaboration and data sharing.

Use of a Liaison-Mediated Referral Strategy and Participation in Cardiac Rehabilitation After Percutaneous Coronary Intervention.

Cardiac rehabilitation (CR) improves outcomes following percutaneous coronary intervention (PCI) but remains underutilized. A liaison-mediated referral (LMR), where a health care professional explains CR's benefits, addresses barriers to participation, and places a referral before discharge, may promote CR use. Our objective was to assess the impact of an LMR on CR participation after PCI. This was a retrospective study of patients who underwent PCI across 48 hospitals in Michigan between January 2021 and April 2022 and referred to CR before discharge. Clinical registry data were linked to administrative claims to identify the primary outcome, CR participation, defined as ≥1 CR session within 90 days of discharge. Bayesian hierarchical logistic regression was used to compare CR participation between patients with and without an LMR. For the secondary outcome, frailty proportional hazard modeling compared days elapsed between discharge and first CR session between liaison cohorts. Among 9023 patients referred to CR after PCI, 4323 (47.9%) underwent an LMR (mean age, 69.3 [SD=11] years; 68.3% male) and 3390 (36.7%) attended ≥1 CR session within 90 days of discharge. The LMR cohort had a higher unadjusted CR participation rate (43.1% [95% CI, 41.5%-44.6%] versus 32.4% [95% CI, 31.1%-33.8%]; P<0.001), a higher adjusted odds ratio of attending ≥1 CR session (adjusted odds ratio, 1.21; 95% credible interval, 1.07-1.38), and a shorter delay in attending the first CR session compared with the non-LMR cohort (28 [interquartile range, 19-42] versus 33 [interquartile range, 21-47] days; P<0.001). An LMR was associated with higher odds of CR participation and may mitigate delays in CR enrollment. This referral strategy may improve CR participation and patient outcomes after PCI.

The Cancer Equity Compass: Interactive maps showing the association between social determinants of health and cancer disparities.

149 Background: Cancer incidence and mortality in Black, Hispanic and Native American populations is over twice that in the White population for some prevalent cancers. A new, publicly available mapping tool, the Cancer Equity Compass (CEC), was developed to inform data-driven initiatives to improve equity by identifying community factors associated with cancer disparities. The tool is comprised of interactive maps that visually reveal correlations between two variables. Development of the tool began with assembling a group of nine advisors with expertise in cancer prevention, treatment and health equity. These experts inform the strategy, data sources, variables of interest, and stakeholder value propositions for the CEC. Methods: The data source for the CEC is a national, multi-level database developed using individual, health system, and community data, aggregated by county. For the three most common cancers in the U.S., breast, prostate and lung, screening and prevalence rates were collected from 2021 Medicare 5% research identifiable files and mortality rates from 2020 SEER Medicare rates. These metrics were each mapped with a variety of social determinants of health (SDOH) variables. Population rates for minorities, education, poverty, income and unemployment, and an air quality measure were from the Area Health Resources File. Environmental risks were derived from the Environmental Justice Index and included environmental burden (ranked 0-17 for pollution, toxic sites, built environment, transportation infrastructure and water pollution), air pollution (ranked 0-4), and social vulnerability (ranked 0-14 across socioeconomic variables). Results: Each map includes one cancer metric and one SDOH variable. Each variable is stratified to show the top quartile, middle 50%, and bottom quartile. The choropleth heat maps, created on Tableau, display 9 colors representing each combination of the three levels (&gt;75%, 25-75%, &lt;25%) for both mapped variables. The CEC currently has 140 maps presenting visualizations of county SDOH associations with cancer disparities. Conclusions: The expert advisors on the project have outlined four avenues for the CEC to aid efforts to improve cancer equity: 1) Enhance diversity in clinical trial recruitment and data registries through targeted site recruitment; 2) Identify high opportunity targets for improving equity and informing solutions; 3) Identify common correlates of disparities within and across U.S. counties to direct priorities for national policy and programs for large-scale impact; and 4) Measure change to support improvement efforts and report impact of equity initiatives. The CEC will be expanded with additional measures including healthcare access. The goal is use by stakeholders and changemakers who can apply the reported data to fuel advocacy efforts and enact positive change.

The Trial Enrollment Diversity Dashboard for Acute Leukemia Clinical Research: Intervention Development and Cohort Analysis.

Participation in acute leukemia clinical trials is inequitable across multiple sociodemographic categories. Tools that provide researchers with performance feedback on the representativeness of the patients they enroll are limited. We aimed to develop an electronic health record (EHR)-based dashboard to provide such feedback and to describe any enrollment inequities uncovered. We created a visual dashboard linking leukemia clinical trial registration and EHR data at the Dana-Farber Cancer Institute. Accuracy of a patient inclusion and assignment algorithm was tested with a target area under the receiver-operator curve (AUROC) of >0.90 against manual review. Demographic metric identification, visualization construction, and dashboard refinement were performed through stakeholder cognitive testing. Analysis of a recent 5-year cohort generated by the final algorithm assessed bivariate associations between enrollment and demographic metrics. Multivariable logistic regression included significant bivariate results. The final algorithm assignment AUROC was 0.98. Metrics were identified and visualizations successfully constructed. Fourteen individuals participated in testing and identified areas for revision: category mergers, denominator filters, and data delivery preferences. In the initial cohort of 1,315 patients, 1,020 (77.6%) had enrolled in any study protocol: 553 (42.1%) in a treatment trial and 936 (71.2%) in a biobanking study. In a multivariable model, older age (odds ratio [OR], 0.83 [95% CI, 0.73 to 0.94]) and Non-Hispanic Black race-ethnicity (OR, 0.38 [95% CI, 0.18 to 0.82]) were associated with lower enrollment, and English primary language with higher enrollment (OR, 2.50 [95% CI, 1.30 to 4.79]). We developed a research participation equity performance feedback dashboard for clinical researchers, and we identified actionable inequities. Next steps include feasibility and efficacy testing as well as implementation.

Cemented Calcar-Guided Short-Stem Prostheses in Geriatric Patients: Short-Term Results from a Prospective Observational Study.

Both cementless and cemented stems have exhibited favorable long-term outcomes in total hip arthroplasty. Nonetheless, in elderly patients, cemented hips offer an advantage due to their reduced risk of periprosthetic fractures. This study aimed to assess the initial outcomes of 28 patients who underwent unilateral cemented total hip arthroplasty utilizing a calcar-guided A2 stem (ARTIQO GmbH, Lüdinghausen, Germany). Various types of antibiotic-loaded bone cement were employed. During follow-up, we recorded demographic data and comorbidities and employed standardized clinical assessment tools, including the Harris Hip Score. Radiographic assessments included preoperative, postoperative, and follow-up imaging to evaluate subsidence, osteolysis, and bone resorption. The results indicated that among the 28 patients, 5 withdrew consent and 2 patients passed away from unrelated causes. Additionally, one prosthesis was explanted due to the undersizing of the cement stopper, which resulted in an inadequate cement mantle. As a result, 20 patients underwent a 1-year follow-up, revealing noteworthy enhancements in clinical scores, with no instances of radiolucent lines or osteolysis. No infections were detected. In summary, our short-term experience with this particular cemented short-stem design yielded promising results, exhibiting excellent functional outcomes, no aseptic loosening attributable to the stem, and no infections. Further clinical studies and registry data are essential to corroborate these findings.

Experience Starting an Addiction Medicine Practice-Based Research Network.

This paper outlines the experience developing Addiction Medicine Practice-Based Research Network (AMNet), which promotes the adoption of patient-reported outcome measures (PROMs) and measurement-based care in outpatient addiction treatment practices and creates a platform for quality improvement and research. From August 2019 to July 2023, the AMNet team selected patient-reported outcome measures for implementation in the American Psychiatric Association's clinical data registry (PsychPRO), recruited addiction medicine providers, and collected PROMs data. AMNet selected 12 PROMs for implementation in PsychPRO. Through July 2023, 1565 providers expressed interest, of whom 216 of the 929 eligible providers (23%) attended an onboarding call/webinar. Two hundred six providers (95%) from 54 practices returned Participation Agreements. Subsequently, 65 providers (32%) from 39 practices withdrew, resulting in 141 (68%) providers from 15 practices. From November 2020 to July 2023, 38 providers submitted PROMs data using 1 of 3 PsychPRO patient portals. Sixteen of the 53 providers (30%) who signed up for the initial portal collected data from 468 patients. As of July 2023, 83 of the 141 providers (59%) opted to submit PROMs data from their own portal or electronic health record. Next steps will include continued recruitment of providers, addressing barriers to data transfer and integrating data from providers' portals into the registry to create a platform for future research.

Landscape of clinical drug development of ADCs used for the pharmacotherapy of cancers: an overview of clinical trial registry data from 2002 to 2022

BackgroundTo provide reference for clinical development of ADCs in the industry, we analyzed the landscape and characteristics of clinical trials about antibody-drug conjugates (ADCs).MethodClinical trials to study ADCs used for the pharmacotherapy of cancers initiated by the sponsor were searched in the Cite line Pharma Intelligence (Trialtrove database), and the landscape and characteristics of these clinical trials were analyzed from multiple perspectives, such as the number, phases, status, indications, and targets of the clinical trials.ResultAs of December 31, 2022, a total of 431 clinical trials have been initiated to study ADCs used for the pharmacotherapy of cancers, and the number of the last 10 years was 5.5 times as large as the first 11 years. These clinical trials involved 47 indications, including breast cancer, lymphoma (lymphoma, non-Hodgkin’s and lymphoma, Hodgkin’s), unspecified solid tumor, bladder cancer and lung cancer (lung, non-small cell cancer and lung, small cell cancer). As for each of these five indications, 50 + clinical trials have been carried out, accounting for as high as 48.50% (454/936). ADCs involve 38 targets, which are relatively concentrated. Among them, ERBB2 (HER2) and TNFRSF8 (CD30) involve in 100 + registered clinical trials, and TNFRSF17 (BCMA), NECTIN4 and CD19 in 10 + trials. The clinical trials for these five targets account for 79.02% (354/448) of the total number. Up to 93.97% (405/431) of these clinical trials explored the correlation between biomarkers and efficacy. Up to 45.91% (292/636) of Lots (lines of treatment) applied in the clinical trials were the second line. Until December 31, 2022, 54.52% (235/431) of the clinical trials have been completed or terminated.ConclusionADCs are a hotspot of research and development in oncology clinical trials, but the indications, targets, phases, and Lot that have been registered are seemingly relatively concentrated at present. This study provides a comprehensive analysis which can assist researchers/developer quickly grasp relevant knowledge to assess a product and also providing new clues and ideas for future research.

Clinical and Economic Burden of Severe Asthma With Low Blood Eosinophil Counts

BackgroundType 2 (T2) low severe asthma phenotype is often a result of corticosteroid-overtreated T2-disease due to persistent symptoms, often not related to asthma, and unlikely to respond to high-dose corticosteroid treatment. ObjectiveThis study aimed to characterise severe asthma patients with low eosinophil counts (<300 cells/μl) and describe their disease burden and treatment across healthcare settings in the UK. MethodsA retrospective cohort study of severe asthma patients using linked Clinical Practice Research Datalink (CPRD) Aurum-Hospital Episode Statistics (HES) and UK Severe Asthma Registry (UKSAR) data indexed patients on latest blood eosinophil count (BEC). Clinical characteristics, treatment patterns, outcomes, and healthcare resource use (HCRU) were described by baseline BEC (≤150 and >150 to <300 cells/μl). ResultsAnalysis included 701 (CPRD-HES) and 1,546 (UKSAR) patients; with 60.5% and 59.4% having BECs ≤150 cells/μl at baseline, respectively. Across BEC groups, the proportion with uncontrolled asthma (≥2 exacerbations) at follow-up (12-months post-index) was 5.4% in CPRD-HES and 45.2% in UKSAR. Maintenance OCS use remained high across BEC groups (CPRD-HES: 29.4%; UKSAR: 51.7%), symptom control remained poor (>200 μg SABA or >500 μg terbutaline/day in CPRD-HES: 48.8%; median ACQ-6 score in UKSAR: 2.0 [1.0-3.3]). HCRU were similar across BEC groups. ConclusionMost patients managed in primary care were infrequent exacerbators, whilst UKSAR patients exacerbated frequently. Large proportions of both patient groups had poor symptom control and continued to receive high levels of maintenance OCS, increasing risk of corticosteroid-induced morbidity. These data highlight the need for rigorous assessment of underlying disease pathology to guide appropriate treatment.

Post-COVID Conditions in US Primary Care: A PRIME Registry Comparison of Patients With COVID-19, Influenza-Like Illness, and Wellness Visits.

COVID-19 is a condition that can lead to other chronic conditions. These conditions are frequently diagnosed in the primary care setting. We used a novel primary care registry to quantify the burden of post-COVID conditions among adult patients with a COVID-19 diagnosis across the United States. We used the American Family Cohort, a national primary care registry, to identify study patients. After propensity score matching, we assessed the prevalence of 17 condition categories individually and cumulatively, comparing patients having COVID-19 in 2020-2021 with (1) historical control patients having influenza-like illness in 2018 and (2) contemporaneous control patients seen for wellness or preventive visits in 2020-2021. We identified 28,215 patients with a COVID-19 diagnosis and 235,953 historical control patients with influenza-like illness. The COVID-19 group had higher prevalences of breathing difficulties (4.2% vs 1.9%), type 2 diabetes (12.0% vs 10.2%), fatigue (3.9% vs 2.2%), and sleep disturbances (3.5% vs 2.4%). There were no differences, however, in the postdiagnosis monthly trend in cumulative morbidity between the COVID-19 patients (trend = 0.026; 95% CI, 0.025-0.027) and the patients with influenza-like illness (trend = 0.026; 95% CI, 0.023-0.027). Relative to contemporaneous wellness control patients, COVID-19 patients had higher prevalences of breathing difficulties and type 2 diabetes. Our findings show a moderate burden of post-COVID conditions in primary care, including breathing difficulties, fatigue, and sleep disturbances. Based on clinical registry data, the prevalence of post-COVID conditions in primary care practices is lower than that reported in subspecialty and hospital settings.

Development and application of Breadth-Depth-Context (BDC), a conceptual framework for measuring technology engagement with a qualified clinical data registry.

Despite the proliferation of dashboards that display performance data derived from Qualified Clinical Data Registries (QCDR), the degree to which clinicians and practices engage with such dashboards has not been well described. We aimed to develop a conceptual framework for assessing user engagement with dashboard technology and to demonstrate its application to a rheumatology QCDR. We developed the BDC (Breadth-Depth-Context) framework, which included concepts of breadth (derived from dashboard sessions), depth (derived from dashboard actions), and context (derived from practice characteristics). We demonstrated its application via user log data from the American College of Rheumatology's Rheumatology Informatics System for Effectiveness (RISE) registry to define engagement profiles and characterize practice-level factors associated with different profiles. We applied the BDC framework to 213 ambulatory practices from the RISE registry in 2020-2021, and classified practices into 4 engagement profiles: not engaged (8%), minimally engaged (39%), moderately engaged (34%), and most engaged (19%). Practices with more patients and with specific electronic health record vendors (eClinicalWorks and eMDs) had a higher likelihood of being in the most engaged group, even after adjusting for other factors. We developed the BDC framework to characterize user engagement with a registry dashboard and demonstrated its use in a specialty QCDR. The application of the BDC framework revealed a wide range of breadth and depth of use and that specific contextual factors were associated with nature of engagement. Going forward, the BDC framework can be used to study engagement with similar dashboards.

Communicating prostate cancer outcomes data to consumers[sbnd] A brief communication

ObjectiveTo translate and communicate outcomes data for prostate cancer from a clinical registry data into a consumer-friendly resource. MethodsFirst, we analyzed real-world data from the South Australian Prostate Cancer Clinical Outcomes Collaborative (SA-PCCOC) registry for men diagnosed from 2008 to 2018 including clinical and functional outcomes following surgery, external beam radiotherapy, brachytherapy, hormone therapy, active surveillance and watchful waiting. These outcomes included overall survival, cancer specific survival, biochemical recurrence, decline in functional outcomes, and transition to active treatment following active surveillance. Second, we translated outcomes into a summary text and pictographic format and present in one document that consumers found easy to understand and interpret. This “Prostate Cancer Outcomes Report Card” was developed in consultation with a consumer advisory group and further improved through exploratory interviews with people affected by prostate cancer, an online survey among the general public, and clinician feedback. ResultsThe 5-year prostate cancer-specific survival rate was 97%. There is a reasonably high chance of cancer returning within 5 years (17% after surgery and 14% after radiotherapy) while 1 in 3 men on active surveillance transitioned to other treatments within 5 years. Sexual function was negatively affected following all treatment types. Men with higher risk disease had a worse prognosis, a higher chance of recurrence and greater decline in physical function. Consumers required trustworthy, comprehensive, simple and up-to-date information collated in one place, and valued having access to this resource. Data on high survival rates were considered reassuring. There were high levels of unmet psychosocial and supportive care needs, especially in relation to mental health and sexual function. The report card was well received by patients and health care workers. ConclusionsThis relatively simple and easily understandable consumer-oriented outcome report serves to better inform men with prostate cancer and facilitate patient-provider communication and shared decision-making.

The 2023 Annual Report of DataDerm: The database of the American Academy of Dermatology

The American Academy of Dermatology launched DataDerm in 2016 as the clinical data registry platform of American Academy of Dermatology. DataDerm has evolved to be the largest database in the world containing information about dermatology patients, capturing information about their course of disease, associated therapeutic interventions, and health outcomes. As of December 31, 2022, DataDerm contained data from 14.2 million unique patients and 53.5 million unique patient visits, with 415 practices representing 1663 clinicians actively participating in DataDerm in 2022. This article is the fourth in a series of Annual Reports about the status of DataDerm. This year's 2023 Annual Report presents the progress DataDerm has made in conjunction with OM1, the data analytics partner of DataDerm, with a special highlight on the longitudinal care of common dermatologic conditions in the registry and a detailed focus on skin cancer. Furthermore, we review the current status of DataDerm as a robust representation of real world specialty data, reflecting the day-to-day dermatologic care of patients over time.

Improving Clinical Registry Data Quality via Linkage With Survival Data From State-Based Population Registries.

Real-world data (RWD) collected on patients treated as part of routine clinical care form the basis of cancer clinical registries. Capturing accurate death data can be challenging, with inaccurate survival data potentially compromising the integrity of registry-based research. Here, we explore the utility of data linkage (DL) to state-based registries to enhance the capture of survival outcomes. We identified consecutive adult patients with brain tumors treated in the state of Victoria from the Brain Tumour Registry Australia: Innovation and Translation (BRAIN) database, who had no recorded date of death and no follow-up within the last 6 months. Full name and date of birth were used to match patients in the BRAIN registry with those in the Victorian Births, Deaths and Marriages (BDM) registry. Overall survival (OS) outcomes were compared pre- and post-DL. Of the 7,346 clinical registry patients, 5,462 (74%) had no date of death and no follow-up recorded within the last 6 months. Of the 5,462 patients, 1,588 (29%) were matched with a date of death in BDM. Factors associated with an increased number of matches were poor prognosis tumors, older age, and social disadvantage. OS was significantly overestimated pre-DL compared with post-DL for the entire cohort (pre- v post-DL: hazard ratio, 1.43; P < .001; median, 29.9 months v 16.7 months) and for most individual tumor types. This finding was present independent of the tumor prognosis. As revealed by linkage with BDM, a high proportion of patients in a brain cancer clinical registry had missing death data, contributed to by informative censoring, inflating OS calculations. DL to pertinent registries on an ongoing basis should be considered to ensure accurate reporting of survival data and interpretation of RWD outcomes.

Co-exposure to gamma-hydroxybutyrate is associated with attenuated neuropsychiatric and stimulant effects of metamfetamine

Introduction Acute metamfetamine toxicity is characterized by stimulant effects and neuropsychiatric disturbance, which is attenuated by gamma-aminobutyric acid type A receptor agonists including benzodiazepines. We utilized clinical registry data to examine the effect of co-exposure to a gamma-aminobutyric acid type B receptor agonist (gamma-hydroxybutyrate) in illicit drug cases with analytically confirmed exposure to metamfetamine. Methods The Emerging Drugs Network of Australia Victoria is an ethics board-approved prospective registry collecting clinical and analytical data (utilising blood samples) on emergency department illicit drug presentations. Comparison groups were defined by analytically confirmed exposure: lone metamfetamine, metamfetamine plus gamma-hydroxybutyrate, metamfetamine plus benzodiazepine, metamfetamine plus gamma-hydroxybutyrate plus benzodiazepine. Cases with co-exposure to other stimulants or sedatives were excluded. Results Median metamfetamine blood concentrations were significantly greater in metamfetamine plus gamma-hydroxybutyrate (n = 153, median = 0.20 mg/L, interquartile range: 0.10–0.32 mg/L, 95 per cent confidence interval: 0.20–0.23 mg/L) and metamfetamine plus gamma-hydroxybutyrate plus benzodiazepine (n = 160, median = 0.20 mg/L, interquartile range: 0.10–0.30 mg/L, 95 per cent confidence interval: 0.20–0.30 mg/L) positive groups compared to gamma-hydroxybutyrate negative groups including metamfetamine (n = 81, median = 0.10 mg/L, interquartile range: 0.05–0.21 mg/L, 95 per cent confidence interval: 0.09–0.18 mg/L) and metamfetamine plus benzodiazepine (n = 73, median = 0.10 mg/L, interquartile range: 0.06–0.20 mg/L, 95 per cent confidence interval: 0.09–0.20 mg/L) groups (P < 0.0004). Presenting heart rate in metamfetamine plus gamma-hydroxybutyrate cases (n = 153, median = 72 beats per minute, interquartile range: 63–86 beats per minute, 95 per cent confidence interval: 70–78 beats per minute) was significantly lower than metamfetamine plus benzodiazepine cases (n = 73, median = 84 beats per minute, interquartile range: 73–98 beats per minute, 95 per cent confidence interval: 80–90 beats per minute, P < 0.0001), and lone metamfetamine cases (n = 81, median = 110 beats per minute, interquartile range: 87–131 beats per minute, 95 per cent confidence interval: 93–120 beats per minute, P < 0.0001). Presenting temperature in metamfetamine plus gamma-hydroxybutyrate cases (median = 35.8 °C, interquartile range: 35.0–36.2 °C, 95 per cent confidence interval 35.6–35.9 °C) was significantly lower than metamfetamine plus benzodiazepine cases (median 36.2 °C, interquartile range 35.7–36.6 °C, 95 per cent confidence interval, 36.0–36.4 °C, P = 0.017), and lone metamfetamine cases (median = 36.5 °C, interquartile range: 35.8–37.1 °C, 95 per cent confidence interval: 36.2–36.7 °C, P < 0.0001). Median presenting systolic blood pressure was significantly (P ≤ 0.001) lower in benzodiazepine positive groups (metamfetamine plus benzodiazepine median = 120 mmHg, interquartile range: 109–132 mmHg, 95 per cent confidence interval: 116–124 mmHg and metamfetamine plus benzodiazepine plus gamma-hydroxybutyrate median = 124 mmHg, interquartile range: 110–137 mmHg, 95 per cent confidence interval: 120–129 mmHg). Incidence of sedation (Glasgow Coma Scale less than 9) was significantly greater in metamfetamine plus gamma-hydroxybutyrate cases (63 per cent) compared to metamfetamine plus benzodiazepine cases (27 per cent, P < 0.0001) and lone metamfetamine cases (15 per cent, P < 0.0001). Incidence of agitation was significantly lower in metamfetamine plus gamma-hydroxybutyrate plus benzodiazepine cases (17 per cent, P < 0.0001) and metamfetamine plus gamma-hydroxybutyrate cases (34 per cent, P = 0.0004) compared to lone metamfetamine cases (58 per cent). Discussion Differences in gamma-aminobutyric acid type A and B receptor physiology may offer a gamma-aminobutyric acid type B agonist-facilitated alternative pharmacodynamic mechanism able to attenuate metamfetamine stimulant and neuropsychiatric toxicity. Conclusion Metamfetamine intoxicated patients with analytically confirmed co-exposure to gamma-hydroxybutyrate had significantly reduced heart rate, body temperature and incidence of agitation compared to patients with lone metamfetamine exposure. Metamfetamine intoxicated patients with analytically confirmed co-exposure to a benzodiazepine had significantly reduced systolic blood pressure compared to patients with lone metamfetamine exposure. We hypothesize that gamma-aminobutyric acid type B receptor agonists may be beneficial in the management of acute metamfetamine toxicity.

Establishment of a registry of clinical data and bioresources for rare nervous system diseases.

Rare diseases are predominantly genetic or inherited, and patients with these conditions frequently exhibit neurological symptoms. Diagnosing and treating many rare diseases is a complex challenge, and their low prevalence complicates the performance of research, which in turn hinders the advancement of therapeutic options. One strategy to address this issue is the creation of national or international registries for rare diseases, which can help researchers monitor and investigate their natural progression. In the Republic of Korea, we established a registry across 5 centers that focuses on 3 rare diseases, all of which are characterized by gait disturbances resulting from motor system dysfunction. The registry will collect clinical information and human bioresources from patients with amyotrophic lateral sclerosis, spinocerebellar ataxia, and hereditary spastic paraplegia. These resources will be stored at ICreaT and the National Biobank of Korea. Once the registry is complete, the data will be made publicly available for further research. Through this registry, our research team is dedicated to identifying genetic variants that are specific to Korean patients, uncovering biomarkers that show a strong correlation with clinical symptoms, and leveraging this information for early diagnosis and the development of treatments.

Glycated Hemoglobin Variability Is Associated With Adverse Outcomes in Patients With Heart Failure Irrespective of Diabetic Status.

The effect of glycated hemoglobin (HbA1c) variability on adverse outcomes in patients with heart failure (HF) is unclear. We aim to investigate the predictive value of HbA1c variability on the risks of all-cause death and HF rehospitalization in patients with HF irrespective of their diabetic status. Using a previously validated territory-wide clinical data registry, HbA1c variability was assessed by average successive variability (ASV) or SD of all HbA1c measurements after HF diagnosis. Multivariable Cox proportional hazards models were used to estimate the adjusted hazard ratio (HR) and its corresponding 95% CI. A total of 65 950 patients with HF were included in the study. Over a median follow-up of 6.7 (interquartile range, 4.0-10.6) years, 34 508 patients died and 52 446 required HF rehospitalization. Every unit increment of variability in HbA1c was significantly associated with higher HF rehospitalization (HR ASV, 1.20 [95% CI, 1.18-1.23]) and all-cause death (HR ASV, 1.50 [95% CI, 1.47-1.53]). Diabetes significantly modified the association between HbA1c variability and outcomes (Pinteraction<0.001). HbA1c variability in patients with HF without diabetes conferred a higher risk of rehospitalization (HR ASV, 1.92 [95% CI, 1.70-2.17] versus HR ASV, 1.19 [95% CI, 1.17-1.21]), and all-cause death (HR ASV, 3.90 [95% CI, 3.31-4.61] versus HR ASV, 1.47 [95% CI, 1.43-1.50] compared with patients with diabetes). HbA1c variability is significantly associated with greater risk of rehospitalization and all-cause death in patients with HF, irrespective of their diabetic status. These observations were more pronounced in patients with HF without diabetes.

Estimating the Prognostic Value of the NTRK Fusion Biomarker for Comparative Effectiveness Research in The Netherlands.

We evaluated the prognostic value of the neurotrophic tyrosine receptor kinase (NTRK) gene fusions by comparing the survival of patients with NTRK+ tumours with patients without NTRK+ tumours. We used genomic and clinical registry data from the Center for Personalized Cancer Treatment (CPCT-02) study containing a cohort of cancer patients who were treated in Dutch clinical practice between 2012 and 2020. We performed a propensity score matching analysis, where NTRK+ patients were matched to NTRK- patients in a 1:4 ratio. We subsequently analysed the survival of the matched sample of NTRK+ and NTRK- patients using the Kaplan-Meier method and Cox regression, and performed an analysis of credibility to evaluate theplausibility of our result. Among 3556 patients from the CPCT-02 study with known tumour location, 24 NTRK+ patients were identified. NTRK+ patients were distributedacross nine different tumour types: bone/soft tissue, breast, colorectal, head and neck, lung, pancreas, prostate, skin and urinary tract. NTRK fusions involving the NTRK3 gene (46%) and NTRK1 gene (33%) were most common. The survival analysis rendered a hazard ratio (HR) of 1.44 (95% CI 0.81-2.55) for NTRK+ patients. Using the point estimates of three prior studies on the prognostic value of NTRK fusions, our finding that the HR is > 1 was deemed plausible. NTRK+ patients may have an increased risk of death compared with NTRK- patients. When using historic control data to assess the comparative effectiveness of TRK inhibitors, the prognostic value of the NTRK fusion biomarker should therefore be accounted for.

Considerations for the use of biochemical laboratory registry data in clinical and public health research

ObjectivesTo inform researchers of central considerations and limitations when applying biochemical laboratory-generated registry data in clinical and public health research. Study Design and SettingAfter review of literature on registry-based studies and the utilization of clinical laboratory registry data, relevant paragraphs and their applicability toward the creation of considerations for the use of biochemical registry data in research were evaluated. This led to the creation of an initial ten considerations. These were elaborated, edited, and merged after several read-throughs by all authors and discussed thoroughly under influence by the authors’ personal experiences with laboratory databases and research registries in Denmark, leading to the formulation of five central considerations with corresponding items and illustrative examples. ResultsWe recommend that the following considerations should be addressed in studies relying on biochemical laboratory-generated registry data: why are biochemical laboratory data relevant to examine the hypothesis, and how were the variable(s) utilized in the study? What were the primary indications for specimen collection in the study population of interest? Were there any pre-analytical circumstances that could influence the test results? Are data comparable between producing laboratories and within the single laboratory over time? Is the database representative in terms of completeness of study populations and key variables? ConclusionIt is crucial to address key errors in laboratory registry data and acknowledge potential limitations.