Diagnosis Codes Research Articles

Impact of CCR5Δ32 on the risk of infection, Staphylococcus aureus carriage, and plasma concentrations of chemokines in Danish blood donors

The CC chemokine receptor 5 (CCR5) is a suggested receptor for Staphylococcus aureus leukotoxin ED. Homozygosity for the Δ32 deletion (CCR5Δ32) protects against human immunodeficiency virus infection and possibly also against leukotoxin ED. We examined the impact of CCR5Δ32 on the susceptibility to S.aureus infection, all-cause infections, and S.aureus nasal carriage, respectively, and on the concentrations of circulating chemokines in blood donors. We included 95,406 participants from the Danish Blood Donor Study (DBDS) genotyped for >650,000 single nucleotide polymorphisms. The CCR5Δ32 (rs333, MAF: 0.12) was imputed from a reference panel and validated. Infectious outcomes were identified by diagnosis codes and redeemed prescription of antibiotics in national health registers. Data on S.aureus nasal carriage and forty-seven inflammatory biomarkers were available for 6721 and 7811 participants, respectively. Cox, logistic, and linear regression models adjusted for relevant confounders were used to explore said associations. During more than 700,000 person-years of observation, we found that CCR5Δ32 was associated with neither an increased risk of redeemed dicloxacillin, hospital-treated S.aureus-associated infection (replicated in 345,996 Icelanders), redeemed antibiotics, all-cause infection, and nor with S.aureus nasal carriage. We discovered an association between CCR5Δ32 and elevated CCL4 concentrations, which were 1.26-fold higher in Δ32-heterozygotes (95%-CI: 1.23-1.30) and 2.64-fold higher in Δ32-homozygotes (95%-CI: 2.41-2.90) compared with wildtype homozygotes. Conversely, concentrations of CCL2, CXCL-10, and CCL11 were slightly lower among Δ32-heterozygotes. Results from this CCR5Δ32 high-prevalent cohort do not support the idea that CCR5Δ32 affects the risk of S.aureus carriage or infection to any relevant degree, in this northern European context. CCL4 was the main chemokine affected by CCR5Δ32 and was observed in higher concentration among Δ32-carriers. This study cannot rule out that S.aureus is a previous driver of CCR5Δ32 selection. The Health Research Fund of Central Denmark Region, Aarhus University, Danish Administrative Regions, Bio- and Genome Bank Denmark, Danish Blood Donor Research Foundation, Aase & Ejnar Danielsens Foundation, Højmosegård Grant, National Institute of Allergy and Infectious Diseases, and A.P. Møller Foundation for the Advancement of Medical Science.

Trends in Medical Encounters Involving Cannabis-Related Disorders Among US Medicare Beneficiaries, 2017-2022.

Objectives. To characterize cannabis-related disorder medical encounter trends in the US Medicare population during 2017 to 2022. Methods. We conducted a descriptive study, which included 56 624 432 beneficiaries aged 65 years or older and 10 247 953 aged 18 to 64 years with disability. All were continuously enrolled in Medicare (Fee-for-Service or Advantage) for 183 or more days before the first day of the calendar year. We identified cannabis-related disorder encounters using International Classification of Diseases, 10th Revision, Clinical Modification diagnosis codes and computed annual encounter rates per 10 000 beneficiaries. We used the Mann-Kendall test to analyze trends over time. Results. Annual cannabis-related disorder encounter trends among beneficiaries aged 65 years or older ranged from 15.9 (95% confidence interval [CI] = 15.8, 16.0) to 39.3 (95% CI = 39.1, 39.5) per 10 000. Rates among beneficiaries aged 18 to 64 years with disability ranged from 274.8 (95% CI = 273.6, 276.0) to 373.7 (95% CI = 372.3, 375.2) per 10 000. Rates increased over time across both groups, with average annual increases of 4.3 (95% CI = 3.3, 5.3; P = .01) and 17.1 (95% CI = 11.0, 23.2; P = .02) per 10 000, respectively. Conclusions. Further work is needed to explore the impact of coexisting medical conditions on outcomes that result from cannabis-related disorders. (Am J Public Health. 2024;114(S8):S694-S697. https://doi.org/10.2105/AJPH.2024.307729).

Impact of quality of care on outcomes in survivors of stroke with aphasia: A linked registry and hospital data observational study

BackgroundThe impact of hospital care quality on patient outcomes in post-stroke aphasia remains unclear. We investigated the impact of nationally-endorsed acute stroke treatments on outcomes post-stroke, by aphasia status. MethodsPatient-level data from the Australian Stroke Clinical Registry (2009–2013) linked to national deaths, hospital emergency presentations and admissions data were used. Aphasia was identified for the index stroke event (ICD-10 diagnosis code R47.0). Impact of receiving an optimal stroke care bundle (stroke unit care, antihypertensive medication at discharge and discharge care plan) and an acute ischemic stroke (AIS) care bundle (stroke unit care, intravenous thrombolysis and aspirin within 48 h of admission) on outcomes were analysed using multivariable regression models with propensity score adjustment. ResultsThe study included 12,690 patients with a median age of 76, 54 % male, and 26 % with aphasia. Non-receipt of the optimal stroke care bundle was associated with worse survival, compared to optimal care, in people with aphasia (HR: 3.37; 95 % CI 2.10, 5.40; p < 0.05) and without aphasia (HR: 2.10; 95 % CI 1.19, 3.69; p < 0.05). Notably, the dose-response effect on survival was more pronounced in individuals with aphasia. In those who received the AIS care bundle, readmission within 12 months was greater in those without aphasia (vs aphasia, p-value interaction = 0.001), whereas survival was similar (p-value interaction = 0.731). ConclusionsSurvivors of stroke with aphasia who did not receive the optimal stroke care bundle, had worse survival at 12 months post-stroke. Ensuring eligible patients receive the optimal stroke care bundle is crucial for improving their 12-month survival.

Association Between Congenital Heart Disease-Related Diagnosis Codes and Trauma Surgery Outcomes.

Congenital heart disease (CHD) is one the most common congenital anomalies, with a prevalence of 8-10 cases per 1000 live births in the United States. Congenital heart disease has been recognized as a risk factor for poor perioperative and postoperative outcomes in non-cardiac surgery. We aimed to determine if documentation of CHD-related diagnosis codes was associated with similar risks for trauma surgery. Data were acquired from the 2010-2019 American College of Surgeons' Trauma Quality Programs Participant Use Files. This study included trauma patients of all ages with one or more surgical procedures and at least one documented non-trauma (comorbidity) International Classification of Diseases code. Patients were stratified based on presence of CHD-related comorbidity codes vs any other comorbidity. Outcomes included mortality, hospital length of stay (LOS), discharge disposition, and in-hospital complications. Using 1:1 propensity score matching, we matched 215 cases with CHD-related comorbid diagnoses to non-CHD controls. Compared to patients with other comorbidities, patients with CHD-related comorbidites were less likely to be discharged home to self-care (odds ratio: 0.44, 95% confidence interval [CI]: 0.25, 078 P = .005) and tended to have prolonged hospital LOS (incidence rate ratio [IRR]: 1.06, 95% CI: 1.001, 1.13, P = .046). We present the first quantitative multicenter analysis correlating documentation of comorbid CHD-related diagnoses with higher risk of adverse outcomes after trauma surgery. These results support the need to routinely acknowledge and document CHD as comorbidity in trauma admissions that could lead to surgical intervention and for trauma centers to prepare for patients with a possible CHD comorbidity.

Emergency Medical Services and Police Utilization for Pediatric Mental and Behavioral Health Concerns Within a Large Hospital System

Objective This study aimed to compare emergency medical services (EMS) and police utilization trends, epidemiology, and emergency department (ED) outcomes between pediatric patients with mental or behavioral health (MBH) emergencies and those with non-MBH concerns transported to a large children's hospital system. Methods This was a retrospective cohort study of patients aged 5 to 18 years transported via EMS and police to two EDs affiliated with a children's hospital from January 2012 through December 2020. Data were abstracted from electronic hospital records. Encounters for MBH emergencies were identified using diagnostic codes and chief complaints. Trends of EMS and police transports of patients with MBH emergencies were examined. Patient demographics and ED outcomes were compared between children presenting with MBH emergencies and those with non-MBH concerns. Results During the 9-year study period, out of 40,663 transports to the EDs, 36,137 (89%) arrived via EMS, and 4,526 (11%) arrived via police. A total of 10,250 (28.4%) EMS transports were for MBH emergencies. The volume of patients transported by EMS for MBH emergencies increased by 1.4% per year (P &lt; 0.01) with no significant change in total EMS patient volumes. Patients with MBH emergencies transported by EMS were more likely to be older, female, of White race, and publicly insured; require restraint in the ED; and be admitted (P &lt; 0.001). Of police transports, 4153 (91.8%) were for MBH emergencies, with no statistical change in the proportion of police transports that were for MBH emergencies. Police-transported MBH patients compared to non-MBH police-transported patients were more likely to be younger, female, and of White race (P &lt; 0.001); 8.7% required mechanical/physical restraints in ED, 6.7% required pharmacologic restraint medications in ED, and 53% were admitted. Conclusions The proportion of pediatric transports for MBH emergencies by EMS is rising and comprises the majority of police transports. Distinct from non-MBH pediatric patients transported, MBH patients necessitate significant ED resources, including ED-administered restraints and admission, highlighting their unique burden on the prehospital and ED systems.

Electronic Health Record Phenotyping of Pediatric Suicide-Related Emergency Department Visits.

Suicide is a leading cause of death among young people. Accurate detection of self-injurious thoughts and behaviors (SITB) underpins equity in youth suicide prevention. To compare methods of detecting SITB using structured electronic health information and measure algorithmic performance across demographics. This cross-sectional study used medical records among youths aged 6 to 17 years with at least 1 mental health-related emergency department (ED) visit in 2017 to 2019 to an academic health system in Southern California serving 787 000 unique individuals each year. Analyses were conducted between January and September 2023. Multiexpert electronic health record review ascertained the presence of SITB using the Columbia Classification Algorithm of Suicide Assessment. Random forest classifiers with nested cross-validation were developed using (1) International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) codes for nonfatal suicide attempt and self-harm and chief concern and (2) all available structured data, including diagnoses, medications, and laboratory tests. Detection performance was assessed overall and stratified by age group, sex, and race and ethnicity. The sample comprised 2702 unique youths with an MH-related ED visit (1384 youths who identified as female [51.2%]; 131 Asian [4.8%], 266 Black [9.8%], 719 Hispanic [26.6%], 1319 White [48.8%], and 233 other race [8.6%]; median [IQR] age, 14 [12-16] years), including 898 children and 1804 adolescents. Approximately half of visits were related to SITB (1286 visits [47.6%]). Sensitivity of SITB detection using only codes and chief concern varied by age group and increased until age 15 years (6-9 years: 59.3% [95% CI, 48.5%-69.5%]; 10-12 years: 69.0% [95% CI, 63.8%-73.9%]; 13-15 years: 88.4% [95% CI, 85.1%-91.2%]; 16-17 years: 83.1% [95% CI, 79.1%-86.6%]), while specificity remained constant. The area under the receiver operating characteristic curve (AUROC) was lower among preadolescents (0.841 [95% CI, 0.815-0.867]) and male (0.869 [95% CI, 0.848-0.890]), Black (0.859 [95% CI, 0.813-0.905]), and Hispanic (0.861 [95% CI, 0.831-0.891]) youths compared with adolescents (0.925 [95% CI, 0.912-0.938]), female youths (0.923 [95% CI, 0.909-0.937]), and youths of other races and ethnicities (eg, White: 0.901 [95% CI, 0.884-0.918]). Augmented classification (ie, using all available structured data) outperformed classification with codes and chief concern alone (AUROC, 0.975 [95% CI, 0.968-0.980] vs 0.894 [95% CI, 0.882-0.905]; P < .001). In this study, diagnostic codes and chief concern underestimated SITB prevalence, particularly among minoritized youths. These results suggest that priority on algorithmic fairness in suicide prevention strategies must extend to accurate detection of youths with suicide-related emergencies.

Digitalising the past decades: automated ICD-10 coding of unstructured free text dermatological diagnoses

BackgroundCurrent digital medical databases record systematically coded diagnoses, but many legacy databases are full of hand-written, free text diagnoses, which can only be meaningfully analysed after mapping them to a coding system. While diagnoses can be extracted from full medical notes with good accuracy, no algorithm using only an unstructured free text diagnosis with no additional data has been published to date.Objectives/methodsTherefore, we sought to create an algorithm which maps hand-written German diagnoses from our clinical photography database to ICD-10 diagnosis codes, validate its output manually by dermatologists and analyse diagnosis counts over time as a proof-of-concept of its application.ResultsOur rule-based algorithm mapped 50,884 unprocessed hand-written German free-text diagnoses covering five decades to ICD-10 codes, while reaching an accuracy of 82% against 817 dermatologist-validated diagnoses. Out of 41,021 data points with the highest algorithm confidence the top 3 identified diagnosis classes were psoriasis, eczema, and non-melanoma skin cancer. The number of ICD-10 codes belonging to chronic inflammatory diseases showed a seasonal pattern with peaks in July, and when analysed aggregated by year, peaks correlated to events such as new therapy classes for these diseases.ConclusionUsing the presented algorithm, it is possible to reliably match hand-written free text of German dermatological diagnoses to ICD-10 codes, thus enabling systematic analysis of legacy databases, making past medical knowledge accessible to today’s patient care.

Development of the Unbiased Disease Network Using Health Insurance Claims Big Data in South Korea

Abstract Background Research on the overall relationship between disease is needed. The disease network model can comprehensively show the complex relationships between diseases and progression patterns. Existing disease network studies were estimated by univariate relative risks. We aim to develop the unbiased disease network. Methods We used NHIS national data of 50 million patients, collected from 2008 to 2022. We used only the primary diagnosis codes (three-digit codes) and defined 603 disease categories based on the special tabulation list for morbidity in the detailed subcategories of ICD-10, prior research, and the frequency of diseases in the dataset. To develop a more unbiased disease network, we first adjusted for age, sex, period, season, and encounter type, then added the confounding disease exposure according to the Directed Acyclic Graph (DAG) and performed Poisson regression to estimate relative risk (RR) applying Inverse Probability Weighting (IPW). We identified statistically significant disease pairs (RR &amp;gt; 1.10, p &amp;lt; 0.001) and repeated the IPW analysis up to the third round because the network would be updated every round. The significant disease pairs identified in the last round were connected to develop the overall network and subnetworks by age and sex. Results We repeated the process up to the third round for all 346,948 disease pairs and fitted 9,024 pairs as significant. We identified general population disease network and subnetwork per age and sex subgroups. Conclusions These disease networks represented the overall progression relationship between diagnosis codes. Key messages • We developed the unbiased disease network that shows progression patterns by adjusting for confounders and using IPW. • The disease network can be used to extract features from various diagnosis codes in EHR/Claims data, analyze causal effects, and predict disease or healthcare usage using RR or graph embedding.

Body Mass Index and Postacute Sequelae of SARS-CoV-2 Infection in Children and Young Adults.

Obesity is associated with increased severity of COVID-19. Whether obesity is associated with an increased risk of post-acute sequelae of SARS-CoV-2 infection (PASC) among pediatric populations, independent of its association with acute infection severity, is unclear. To quantify the association of body mass index (BMI) status before SARS-CoV-2 infection with pediatric PASC risk, controlling for acute infection severity. This retrospective cohort study occurred at 26 US children's hospitals from March 2020 to May 2023 with a minimum follow-up of 179 days. Eligible participants included children and young adults aged 5 to 20 years with SARS-CoV-2 infection. Data analysis was conducted from October 2023 to January 2024. BMI status assessed within 18 months before infection; the measure closest to the index date was selected. The BMI categories included healthy weight (≥5th to <85th percentile for those aged 5-19 years or ≥18.5 to <25 for those aged >19 years), overweight (≥85th to <95th percentile for those aged 5-19 years or ≥25 to <30 for for those aged >19 years), obesity (≥95th percentile to <120% of the 95th percentile for for those aged 5-19 years or ≥30 to <40 for those aged >19 years), and severe obesity (≥120% of the 95th percentile for those aged 5-19 years or ≥40 for those aged >19 years). To identify PASC, a diagnostic code specific for post-COVID-19 conditions was used and a second approach used clusters of symptoms and conditions that constitute the PASC phenotype. Relative risk (RR) for the association of BMI with PASC was quantified by Poisson regression models, adjusting for sociodemographic, acute COVID severity, and other clinical factors. A total of 172 136 participants (mean [SD] age at BMI assessment 12.6 [4.4] years; mean [SD] age at cohort entry, 13.1 [4.4] years; 90 187 female [52.4%]) were included. Compared with participants with healthy weight, those with obesity had a 25.4% increased risk of PASC (RR, 1.25; 95% CI, 1.06-1.48) and those with severe obesity had a 42.1% increased risk of PASC (RR, 1.42; 95% CI, 1.25-1.61) when identified using the diagnostic code. Compared with those with healthy weight, there was an increased risk for any occurrences of PASC symptoms and conditions among those with obesity (RR, 1.11; 95% CI, 1.06-1.15) and severe obesity (RR, 1.17; 95% CI, 1.14-1.21), and the association held when assessing total incident occurrences among those with overweight (RR, 1.05; 95% CI, 1.00-1.11), obesity (RR, 1.13; 95% CI, 1.09-1.19), and severe obesity (RR, 1.18; 95% CI, 1.14-1.22). In this cohort study, elevated BMI was associated with a significantly increased PASC risk in a dose-dependent manner, highlighting the need for targeted care to prevent chronic conditions in at-risk children and young adults.

Contemporary description of cardiac manifestations in ATTR amyloidosis: results from the multi-country OverTTuRe study

Abstract Background In transthyretin (ATTR) amyloidosis, amyloid fibrils accumulate in the myocardium, resulting in cardiac manifestations that can ultimately be fatal. The diverse presentation of this condition often results in prolonged diagnostic journeys for patients before they receive a definitive diagnosis of ATTR amyloidosis and treatment. Purpose To delineate the demographic and clinical characteristics of patients diagnosed with ATTR amyloidosis by cardiac manifestations, and to examine the duration from the first recorded cardiac manifestation to diagnosis. Methods OverTTuRe is a multi-country study generating real-world evidence from a cohort of patients identified as having ATTR amyloidosis between 2017-2022. Data were extracted from the US (Optum’s de-identified Clinformatics Data Mart Database) and Japan (Medical Data Vision Database). Additional analyses from European countries are ongoing. Patients aged ≥18 years with a recorded ICD-10 diagnosis code for ATTR amyloidosis (all phenotypes) or record for an ATTR-specific treatment were included. The index date was defined as first recorded date of diagnosis or ATTR-specific treatment. Patients with a diagnostic code or treatment indicative of secondary (AA) amyloidosis or light chain (AL) amyloidosis were excluded. Results 17,720 patients (median age: 75 years; 48.3% males) with ATTR amyloidosis were identified from the US and 4,690 from Japan (median age: 77 years; 57.0% males). Among individuals with 5 years of any available data prior to ATTR amyloidosis diagnosis (US: 9,147 [51.6%]; Japan: 2,600 [55.4%]), the most frequent initial cardiac manifestation ahead of ATTR amyloidosis was heart failure (US: 30.3%; Japan: 42.0%) followed by atrial fibrillation (21.9%) and cardiomyopathy (21.7%) in the US, and angina (21.6%) and atrial fibrillation (18.7%) in Japan. Among patients with 5 years of any available data before diagnosis plus cardiac manifestations, there were higher proportions of males than females and older individuals (Table). Median time from the earliest recording of any cardiac manifestation to the diagnosis of ATTR amyloidosis was 2.4 years (IQR: 0.9, 3.9) in the US and 1.2 years (IQR: 0.1, 3.2) in Japan. Median time to diagnosis increased with age and was similar across sexes in the US, whilst females in Japan had longer median time to diagnosis. Among the cardiac manifestations (heart failure, atrial fibrillation, cardiomyopathy, angina, aortic valve stenosis), 52.5% of patients in Japan had at least 2 manifestations, whilst in the US 59.4% of patients had more than 2 manifestations. Conclusions These findings highlight the prevalence of cardiac manifestations such as heart failure, in patients identified as having ATTR amyloidosis, particularly among men and elderly individuals. The observed delay in diagnosis of ATTR amyloidosis illustrates the importance of increased awareness to support early recognition and treatment to limit adverse clinical outcomes.

Electrocardiogram-based artificial intelligence to identify prevalent coronary artery disease

Abstract Background Coronary artery disease (CAD) often goes undetected for years before it manifests and results in substantial morbidity and mortality. Some patients have neither typical risk factors nor symptomatic angina despite progressive disease. Purpose Develop a deep-learning model to detect prevalent CAD and identify people at risk for adverse events using electrocardiograms (ECG) in a primary care setting. Methods We developed a convolutional neural network using 12-lead ECG waveforms to discriminate the presence of CAD defined using diagnostic codes ("ECG2CAD"). ECG2CAD was trained on 764,670 ECGs from 137,199 individuals at the Massachusetts General Hospital (MGH). Model performance for discrimination of prevalent CAD was measured using AUROC and AUPRC, and compared against a model comprising age and sex, as well as the Pooled Cohort Equations (PCE), in three test sets independent of model training: MGH, Brigham and Women’s Hospital (BWH) and UK Biobank. ECG2CAD was assessed across subgroups of age, sex and self-reported ethnicity and for incident CAD-related events in the BWH primary care subset. Results ECG2CAD was evaluated in MGH (N=18,706 [N=6,051 cases], age 57±16 years), BWH (N=88,270 [N=27,898 cases], age 57±16 years), and UK Biobank (N=42,147 [N=1,509 cases], age 65±8 years). ECG2CAD consistently discriminated prevalent CAD (MGH: AUROC 0.782, AUPRC 0.639; BWH: AUROC 0.747, AUPRC 0.588; UK Biobank: AUROC 0.760, AUPRC 0.155) and incrementally improved upon both a model based on age and sex (p&amp;lt;0.01) and the PCE (p&amp;lt;0.01) in MGH and BWH. In the BWH primary care subset (N=51,808), model performance was consistent in subgroups defined by age, sex and self-reported ethnicity/race. The incorporation of ECG2CAD in addition to age and sex consistently improved discrimination (AUROC delta of 0.011-0.086) in all subgroups. In the BWH primary care subset with over 10 years of follow-up, we observed that either the presence of ECG2CAD-predicted CAD (HR 2.18, 95% CI 2.00-2.38, P&amp;lt;0.001) and ICD-based known CAD (HR 2.13, 95% CI 1.86-2.45, P&amp;lt;0.001) were associated with increased risk for incident myocardial infarction. The presence of both definitions was associated with an almost five-fold increase in risk (HR 4.97, 95% CI 4.51-5.48, P&amp;lt;0.001). The risk of incident adverse events was highest among people in the top quintile of ECG-based predicted risk (high risk) compared with people from quintile 4-2 (intermediate risk) or the lowest quintile (low risk), even when excluding those with known prevalent CAD at baseline. Conclusions Artificial intelligence-enabled analysis of the 12-lead ECG may facilitate efficient identification of individuals with possible undiagnosed CAD and inform downstream testing and preventive measures.

COVID-19 vaccine associated myocarditis in Norway - a nationwide validation study

Abstract Background The SARS-CoV-2 pandemic led to worldwide initiation of vaccination campaigns. The new mRNA vaccines were unexpectedly associated with vaccine-associated myocarditis (VAM). The incidence and severity of VAM has not been validated in a nation-wide and well-defined population. From December 2020 onwards the mRNA vaccines Comirnaty and Spikevax have been in widespread use in Norway. The National Patient Register (NPR) includes all hospital contacts with corresponding diagnostic codes (ICD-10), and all vaccinations are registered in the Norwegian Immunization Register (SYSVAK). Purpose We aimed to identify and validate all cases of suspected COVID-19 VAM in Norway during the national vaccination campaign between 2020-22. Methods We identified all cases of myocarditis acquired within 90 days of a COVID-19 vaccination through linkage of diagnostic codes for myocarditis in NPR and vaccination data in SYSVAK. Cases were included from December 2020 through April 2022. We assessed medical records, cardiac imaging, and biochemistry to retrospectively validate all myocarditis cases. The Brighton Criteria (international criteria for myocarditis diagnosis following immunization with defining levels of diagnostic certainty) were used to confirm the VAM diagnosis. Results From December 2020 to April 2022, 4 114 750 unique subjects (2 036 792 men and 2 077 958 women, median age first dose 47 years) above 16 years of age, received 10 915 098 unique doses of COVID-19 vaccines (8 651 703[79%] Comirnaty and 2 263 395[21%] Spikevax). Of 277 cases of myocarditis identified in NPR&amp;lt;90 days after receiving a COVID-19 vaccine, 176(64%) were validated as VAM (78 definite, 90 probable, and 8 possible VAM). Among the patients with VAM, 137(78%) were men with median age 30(IQR 24-47) years, and 39(22%) were women with median age 54(IQR 32-65) years. There were 4 cases of VAM per 100 000 vaccinated subjects: 7 per 100 000 men and 2 per 100 000 women. Sixty-three percent of VAM occurred after the second mRNA vaccine dose. There were 3.3 cases of VAM per 100 000 unique doses of Spikevax compared to 1.1 per 100 000 unique doses of Comirnaty. The most common time interval from vaccination to VAM was 3 days and occurred in 30 patients (17.3% of VAM, 93% men), and 34% of VAM (90% men) occurred during the first 5 days from vaccination(Figure). Median duration of hospital stay was 4(IQR 3-5) days, with only 7(4%) patients needing intensive care and 1 myocarditis related patient death during hospitalization. Conclusions In this unique nationwide study including all COVID-19 vaccinated subjects in Norway from 2020-22 we found 4 cases of VAM per 100 000 vaccinated subjects. The majority of VAM occurred in young men. Interestingly, women presented later than men with VAM and most frequently at middle to older age. The occurrence of this unexpected serious adverse event underscores the importance of large studies in broad populations in future vaccine programs.

Detecting Unrecognized Dementia Using Deep Learning Methods with Korean National Claims Data

Abstract Background Dementia is one of the leading causes of death in elderly people. In Korea, the government supports dementia screening for people aged 60 and older, but it is not a population-based organized screening program. It is difficult to achieve early diagnosis and early treatment. The objective of this study is to detect unrecognized dementia using Korean National Claims Data for early diagnosis. Methods This study used the National Health Insurance Claims data in Korea. The case group is the new dementia visit as an unrecognized group, while the control group was randomly selected from the general population without dementia. The predictors included health utilization, socioeconomic and demographic, procedure codes, diagnostic codes and health screenings data. The health utilization variables included length of stay, the number of outpatient visits, health expenditures and other encounter information. All medical utilization data was aggregated monthly. In the case group, 12 months of data from 6-month or 2-years before the onset of dementia were used. In the control group, 12 months of data from randomly selected time point were included. Transformer, embedding methods, and Time2Vec were used as the deep learning methods. This study included 453,306 incidents of dementia, representing almost all cases reported from 2010 to 2019 in Korea. The control group consisted of 669,873. Results After training the deep learning prediction model, the AUC for 6-month dementia prediction on the test dataset was 0.87, and for 2-year dementia prediction, it was 0.76. The most important variables were health utilization variables, especially health expenditures. The health utilization trajectories of the case group were significantly different from those of the control group. Conclusions Based on the claims data, we could detect unrecognized dementia case. We can extend the model to other chronic disease such as cancer and stroke, which are significant burden of disease. Key messages • Screening in healthcare facilities or using lab test results would be more accurate, but it would be difficult to apply to a large population due to the cost-effectiveness and timeliness constraints. • On the other hand, the detection model using the existing claims data would be helpful to to develop cost-effective mass screening program. It can cover the weakness of current screening program.

Patient characteristics and incidence of cardiac amyloidosis: an observational study in the UK clinical setting using electronic health records

Abstract Background Cardiac amyloidosis (CA) is associated with a high mortality rate due to sudden or progressive heart failure. It is often misdiagnosed due to non-specific symptoms, and its true incidence and prevalence in the United Kingdom (UK) remain uncertain. Purpose To describe patient characteristics and incidence of CA in the UK clinical setting using electronic health records. Methods In this retrospective observational study, anonymised, linked primary and secondary care data (Clinical Practice Research Datalink, CPRD and Hospital Episode Statistics, HES) were used to describe individuals diagnosed with CA. The CPRD database contains de-identified patient data sourced from a sample of general practitioner (GP) practices in the UK. Patients aged 18 years and older with a recorded Read or SNOMED-CT diagnosis code for CA or record of treatment with tafamidis (a licensed but not reimbursed treatment for transthyretin amyloid cardiomyopathy, ATTR-CM in the UK) in the period between January 2004 to December 2021 were included. The index date was defined as the earliest recorded date of CA diagnosis or tafamidis treatment. Demographic and clinical data were summarised using descriptive statistics. Incidence rates were reported per 100,000 person-years (PY). Results There were a total of 3,788 patients with CA (mean age: 67 years; 61% males) of which only 277 were coded as having wild-type transthyretin (ATTRwt) CA in mostly older patients (mean age: 79 years). The low patient counts of ATTRwt amyloidosis could be attributed to the lack of specificity in CA types and the low utilisation of ATTR amyloidosis codes. Heart Failure, essential hypertension and dyspnoea were the most common clinical presentations recorded in the 12 months to first diagnosis code or tafamidis prescription for CA (Table). The incidence of CA varied from 0.75 in 2004 to a peak of 1.96 in 2021, per 100,000 PY; a 2.9-fold increase in newly coded diagnoses in CA. There was a slight decline in the rates in 2020 and 2021 (Figure). Incidence rates in males and females increased over the 17-year period, with males consistently having higher rates than females. The incidence rate in females started from a lower base at 0.62/100,000 PY in 2004, increased by a factor of 1.9 to 1.1/100,000 PY, whereas in males it started at 0.88/100,000 PY and rose by a factor of 2.9 to 2.5 /100,000 PY. Incidence rates in subgroup populations have also been analysed. Conclusions In the UK clinical setting, the incidence rate of newly coded CA increased overall between 2004 and 2021, as well as in both male and female subgroups. The data suggest CA is becoming more common, or that awareness has improved, and there is now an urgent need for enhanced methods of detection, characterisation, and the need for thorough data capture to shape future pathway advancements.

Effect of body mass index on mortality for diabetic patients with aortic stenosis

Abstract Background Several studies suggest an "obesity paradox," associating obesity with better cardiovascular outcomes compared to normal or underweight individuals (1-3). Purpose This study explores the impact of body mass index (BMI) on mortality in patients with diabetic mellitus (DM) and aortic stenosis (AS). Methods This is a retrospective cohort study conducted at a tertiary centre. Between 2014 and 2019, patients with DM who underwent echocardiography were screened (4). Patients were enrolled if AS was diagnosed, according to established guidelines (5). Two echocardiography specialists independently reviewed the echocardiography in the cohort. The index date of the DM-AS cohort was the first AS diagnosis by echocardiography, and detailed data collection methods are described in previous studies (6,7). Patients were categorized as underweight, normal weight, or obese based on BMI (&amp;lt;18.5, 18.5 to 27, and &amp;gt;27 kg/m2, respectively). Outcomes included all-cause mortality, cardiovascular, and non-cardiovascular death, which were adjudicated by a central committee. The occurrence times of the outcomes of interest were determined using diagnosis codes from electronic health records, and medical records were reviewed until the last clinical visit or death. Results Among 74,835 DM patients, 734 had AS. Normal weight comprised 65.5% (n=481), underweight 4.1% (N=30), and 30.4% were obese. With a median follow-up time of 34 months, 285 patients (38.8%) experienced outcomes of death, comprising 93 patients (32.7%) with cardiovascular death and 192 patients (67.3%) with non- cardiovascular death. Underweight patients had significantly higher all-cause mortality (HR 1.96, 95% CI 1.22 – 3.14, p = 0.005), while obese patients had significantly lower mortality (HR 0.79, 95% CI 0.68 - 0.91, p=0.001) compared to the normal group. Regarding etiologies, underweight patients had a higher risk of non- cardiovascular death (HR 2.47, 95% CI 1.44-4.25, p = 0.001), while obese patients had a lower risk of cardiovascular death (HR 0.66, 95% CI 0.50-0.86, p=0.003). Subgroup analysis showed a consistent trend without significant interaction. To elucidate the interaction of BMI as a continuous variable with outcomes, restricted cubic spline analysis was applied. Cardiovascular death showed a negative association with BMI across available BMI levels, and non-cardiovascular death exhibited a U curve, with the lowest hazard ratio occurring when BMI was between 25 to 30. Conclusion Our study underscored the significance of both cardiovascular and non-cardiovascular deaths as crucial contributors to overall mortality in DM patients with AS. Being underweight is associated with increased non- cardiovascular death, while obesity is linked to less cardiovascular death. Proposed mechanisms include reduced frailty, enhanced tolerance to guideline-directed medical therapies (GDMTs), and heightened disease awareness in the obese group (8,9).Kaplan–Meier analysis for outcomesAssociation between BMI and outcomes

Association of a history of acute kidney injury with major adverse cardiovascular events in chronic kidney disease patients

Abstract Background/introduction Acute kidney injury (AKI) is strongly associated with major adverse cardiovascular events (MACE), particularly heart failure, in both general and critically ill populations. A recent study questioned whether this association holds true only for patients without chronic kidney disease (CKD). Purpose To evaluate the association of a history of AKI with MACE in a large real-world CKD population defined using the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Methods A retrospective cohort study was conducted using Merative® Explorys electronic health records (&amp;gt;54 million patients) from Jan 2010 to Dec 2019. Six cohorts of CKD patients (diagnosed or not) were created, one for each stage (1-5). Patients were required to have two consecutive abnormal eGFR, uACR/uPCR results within 3-18 months to determine CKD stage, to have at least a 12-months lookback period, and no history of end-stage kidney disease. CKD classification was not mutually exclusive (individual patients could contribute to multiple stages). Index date was the date of the second abnormal test. History of AKI was defined using ICD diagnosis codes, not through biological changes. We followed each patient until the occurrence of a composite of MACE including death, coronary events [acute coronary syndrome + coronary revascularization], any stroke, hospitalization for heart failure, or loss to follow-up, or for up to 5 years. We used multivariable Cox proportional hazards regression to estimate associations between the history of AKI and the risk of MACE during follow-up, adjusted for the following confounders: age, sex, ethnicity, systolic blood pressure, eGFR, BMI, CV history, diabetes, and any CKD diagnosis at baseline. Results Most of the 969,394 patients included in at least one CKD stage cohort were in stage 3a (see table) and Caucasian. Mean ages were 57-75y and 42%-64% were females across the 5 CKD stages. The prevalence of pre-existing CV disease increased from 24% in stage 1 to 57% in stage 4. The proportion of patients with a history of AKI increased from 4% in stage 1 to 36% in stage 4, as well as, the proportion of patients with a ICD code for CKD diagnosis at baseline (3% to 44%). The 5-year incidence of the composite of MACE increased from 25.1% in stage 1 to 65.8% in stage 5. Death was the most frequent event across all stages. In multivariable analysis, a history of AKI was associated with increased risk of MACE (hazard ratios, HR 1.19 to 1.32), all-cause death (HR 1.12 to 1.86), and hospitalization for Heart Failure (HR 1.59 to 1.98) for all CKD stages, and coronary events for stage 2 to 5 (HR 1.14 to 1.22), but not stroke. Conclusion Patients with CKD and a history of AKI are at higher risk of adverse CV outcomes, especially hospitalization for heart failure. This study suggest that these patients should receive cardio -protective intervention.

Global burden of high-risk cardiovascular patients without prior myocardial infarction or stroke: VESALIUS-REAL - preliminary results from Germany

Abstract Background Clinical trial data has shown that low-density lipoprotein cholesterol (LDL-C) lowering with PCSK9-inhibitors reduced cardiovascular (CV) endpoints in patients with established atherosclerotic cardiovascular disease (ASCVD). Intervening early in patients with high CV risk prior to myocardial infarction (MI) or stroke, while perceived to be less urgent, may result in larger public health benefits. The effect of evolocumab in this population is investigated in a phase-3 clinical trial (NCT03872401: Effect of Evolocumab in Patients at High Cardiovascular Risk Without Prior Myocardial Infarction or Stroke [VESALIUS-CV]). This observational study examines the global burden of VESALIUS-CV-like population in the REAL-World ("VESALIUS-REAL") in eight regions (Germany, Hong Kong, Japan, South Korea, Sweden, Taiwan, UK and US) using a unified protocol across multiple databases. The multi-database study is ongoing, and the current analysis focuses on characteristics of VESALIUS-CV like patients in Germany. Methods Eligibility criteria are shown in the Figure. Data were obtained from the German Disease Analyzer (2013-2022), a representative claims database from Germany. Criteria were aligned with the clinical trial, and real-world definitions were created using diagnosis and procedure codes. Results A total of 195,621 patients were included in the present analysis (Table). At baseline, the median age was 71 years (Q1-Q3: 64-79) and 48% of patients were women. Approximately two-thirds of patients had atherosclerosis (48.5% had coronary artery disease, 13.8% had cerebrovascular disease and 13.8% had peripheral artery disease) and 33.7% had high-risk diabetes mellitus (DM), defined as DM with microvascular complications or chronic insulin use. The median baseline LDL-C was 139 (Q1-Q3: 113-166) mg/dL [3.6 (2.9 - 4.3) mmol/L] and 110,867 patients (57%) had an LDL-C ≥130 mg/dL (≥3.4 mmol/L). Overall, 69% of VESALIUS-CV like patients were receiving no background LLT. Conclusions Despite having atherosclerosis and/or high-risk DM and LDL-C exceeding target thresholds, a large proportion of VESALIUS-CV like patients were not on any LLT in Germany. Final results from VESALIUS-REAL will be able to report if this treatment gap is also observed in other countries.

Adherence to anti-hypertensive therapy with perindopril-based single-pill versus free-pill combinations: a 10-year real-world analysis in Italy

Abstract Background/Introduction Despite the growing availability of blood pressure-lowering drugs, hypertension remains poorly controlled and a significant mortality cause worldwide. The silent course of the disease, suboptimal adherence, and complexity of therapeutic schedules are important factors in reducing the effectiveness of anti-hypertensive treatments at the population level. With the purpose of simplifying patients’ medication self-management, guidelines have strongly endorsed the use of anti-hypertensive therapy with single-pill combinations (SPCs). Perindopril (PER)-based SPCs, including both two- and three-drug combinations, have been available since 2008. Purpose We explored treatment adherence over 10 years in patients receiving PER-based regimens (SPC or free-pill combination) in Italy. Methods A retrospective real-world analysis was conducted on administrative databases covering 6.7 million Italian health-assisted residents. Among adults with hospitalization discharge diagnosis or exemption code for hypertension between 2010 and 2021, those with PER-based prescriptions were identified, considering combinations with amlodipine (AML) and/or indapamide (IND), either as SPC or free-pill or mixed (SPC+separate pill). The index-date (ID) was that of the first prescription of a PER-based regimen throughout the inclusion period. All patients with at least 12 months of available data before and after the ID were included. A cross-sectional analysis evaluated the yearly adherence for the period 2012-2021, calculating the proportion of days covered (PDC) by drug prescriptions on 1-year follow-up (PDC≥80% indicated high-adherence). Results Over 2012-2021, of 121,397 patients on a PER-based therapy, those treated with SPC ranged from 87% (during 2012) to 94.4% (during 2021), while free-pill and SPC+separate pill cohorts represented, respectively, 10.6-3.5% and 2.4-2.1% of all hypertensive patients. Over the decade, the proportion of adherent patients in SPC users was markedly higher than in free-pill and SPC+separate pill cohorts (Fig. 1). The sudden reduction of adherent patients during 2018-2019 was possibly due to a temporary shortage of PER/AML/IND as SPC in Italy from Nov-2018 to Mar-2019. Multivariate analysis showed that over 2012-2021 decade, free-pill and SPC+separate pill regimens resulted in significantly lower adherence (more than 80% reduction) than SPC formulation, while male gender and older age were predictive of better adherence (Table 1). Conclusions These findings from real clinical practice in Italy highlighted a growing attitude from clinicians to prescribe more manageable anti-hypertensive schemes based on SPC formulations, in line with current guidelines. The higher proportion of adherent patients among the users of PER-based SPCs corroborates the importance of alleviating pill burden, that is a key component in blood pressure control, and so in the reduction of hypertensive complications and cardiovascular risk.

Real-world analysis exploring the association between anti-hypertensive therapy with perindopril-based single-pill combinations (SPC) and cardiovascular outcomes and all-cause mortality in Italy

Abstract Background/Introduction A combination of blood pressure (BP)-lowering medications is recommended by guidelines as an effective strategy to obtain rapid and optimal BP control in hypertensive patients. However, the prescription of multiple BP-lowering medications increases the pill burden, potentially reducing medication adherence. Guidelines also recommend using single pill combinations(SPCs) containing ≥2 anti-hypertensive medications as a practical approach to simplify treatment schedules and possibly improve adherence. Yet, real-world evidence on the association between SPC or free combination of BP-lowering medications and hyperthensive patient outcome remains limited. Purpose We compared the association of SPC versus free-pill combination(free) on cardiovascular outcomes and all-cause mortality in hypertensive patients treated with perindopril(PER)-based therapies in real clinical practice in Italy. Methods A retrospective analysis was conducted using administrative databases covering 6.7 million health-assisted Italian residents. Among adults with hospitalization discharge diagnosis or exemption code for hypertension between 2010 and 2021, the study included patients prescribed with a combination of PER with amlodipine(AML) and/or indapamide(IND), either as SPC or free or mixed (SPC plus separate pill) combinations. Results The analysis included 24,476 hypertensive subjects receiving a PER-based therapy, 22,663 (93%) of them using SPC, 1458 (6%) free and 355 (1.4%) mixed. The last cohort was not included in the analysis due to the small sample size (N=355). The patients in the free cohort were significantly older than those in the SPC cohort (69.5±12.3 vs. 64.3±12.2 years, p&amp;lt;0.001), showed a higher number of pre-existing comorbidities (0.5±0.8 vs. 0.4±0.7, p&amp;lt;0.001), and received a larger number of different medications (pill burden: 1.2±1.7 vs. 0.7±1.3, p&amp;lt;0.001). To minimize selection bias, the groups were balanced with propensity score and inverse probability weighting (IPW), adjusting for baseline covariates, including comorbidity profile and pill burden. The IPW-adjusted Kaplan-Meier plots and Cox’s proportional hazard model (Table 1) revealed that, compared with SPC users, patients on free regimens had a significantly increased risk of all-cause mortality (36%, p&amp;lt;0.001), all cardiovascular events (45%, p&amp;lt;0.001), ischemic heart disease (29%, p&amp;lt;0.05), cerebrovascular events (84%, p&amp;lt;0.001), and occurrence of the composite outcome cardiovascular events/all-cause mortality (40%, p&amp;lt;0.001). Conclusions This real-world data from a large Italian administrative dataset suggested that PER-based anti-hypertensive therapy with SPC results in significant clinical benefits in terms of lowered risk of cardiovascular/cerebrovascular events and all-cause mortality. Reducing pill burden and simplifying therapeutic schedules is of crucial importance to maximize the potential benefits derived from the prescription of anti-hypertensive treatment.

Lower rate of ischemic events with PCSK9 inhibition in patients with atherosclerotic cardiovascular disease but without prior ischemic events

Abstract Background Individuals with atherosclerotic cardiovascular disease (ASCVD) without prior ischemic events, such as myocardial infarction (MI), ischemic stroke (IS), or unstable angina (UA) hospitalization, are at very high risk for having an event. Purpose To estimate the impact of PCSK9 inhibitor (PCSK9i) therapy on ischemic events in this population. Methods Patients with ASCVD were initially selected from the Optum Research Database during Jan 2016 to Dec 2022. For selected patients the index (time zero for follow-up) was required to be in a period of ASCVD without prior ischemic events, however patients may have ischemic events after index. Determination of ASCVD and ischemic events was based on diagnosis and procedure codes. For the PCSK9i group, index was initiation of PCSK9i and information before index was examined to ascertain ASCVD and rule out prior ischemic events. For each patient in the PCSK9i group, up to 5 matching patients in the no-PCSK9i group were chosen based on propensity score (PS) distance, with maximum allowable PS distance of 0.1. Among all possible choices for index for the no-PCSK9i patient, the selected one minimized the PS-distance. The primary endpoint was defined as the composite of nonfatal MI, nonfatal IS, and all-cause death. In order to further reduce bias and ensure causally interpretable estimation, the G-computation methodology was employed by marginalizing the conditional treatment effect (as estimated by a Cox model) over the baseline characteristics. Two effects were estimated: intention-to-treat (ITT) where only the treatment assignment at index was considered as the intervention, and per-protocol (PP) where the effect of sustained treatment with PCSK9i over time was estimated. Results A total of 15,067 and 66,470 patients met the selection criteria for the PCSK9i and no-PCSK9i groups, respectively. Baseline characteristics were well-balanced at index. G-computation analysis resulted in estimated survival curves over time in the two groups for the ITT and PP scenarios (Figures 1 and 2). For the ITT scenario, the estimated 5-year event rate was 18.7% (95% confidence interval [CI]: 17.1%–20.1%) in the PCSK9i group and 28.4% (95% CI: 27.7%–29.1%) in the no-PCSK9i group. The implied relative risk reduction (RRR) and absolute risk reduction (ARR) were 34.3% (p&amp;lt;0.001) and 9.7% (p&amp;lt;0.001), respectively, in favor of the PCSK9i group. For the PP scenario, the estimated 5-year event rate was 10.7% (95% CI: 9.7%–11.7%) in the PCSK9i group and 28.8% (95% CI: 28.3%–29.5%) in the no-PCSK9i group. The implied RRR and ARR were 62.7% (p&amp;lt;0.001) and 18.1% (p&amp;lt;0.001), respectively, in favor of the PCSK9i group. Conclusions Initiation of PCSK9i in patients with ASCVD but without prior ischemic events is associated with significantly and substantially lower risk for ischemic events.Event Rates Intention-to-Treat ScenarioEvent Rates Per-Protocol Scenario