Person-years In Patients Research Articles

Atypical hemolytic uremic syndrome in the era of terminal complement inhibition: an observational cohort study

AbstractHistorically, the majority of patients with complement-mediated atypical hemolytic uremic syndrome (CaHUS) progress to end-stage kidney disease (ESKD). Single-arm trials of eculizumab with a short follow-up suggested efficacy. We prove, for the first time to our knowledge, in a genotype matched CaHUS cohort that the 5-year cumulative estimate of ESKD-free survival improved from 39.5% in a control cohort to 85.5% in the eculizumab-treated cohort (hazard ratio, 4.95; 95% confidence interval [CI], 2.75-8.90; P = .000; number needed to treat, 2.17 [95% CI, 1.81-2.73]). The outcome of eculizumab treatment is associated with the underlying genotype. Lower serum creatinine, lower platelet count, lower blood pressure, and younger age at presentation as well as shorter time between presentation and the first dose of eculizumab were associated with estimated glomerular filtration rate >60 ml/min at 6 months in multivariate analysis. The rate of meningococcal infection in the treated cohort was 550 times greater than the background rate in the general population. The relapse rate upon eculizumab withdrawal was 1 per 9.5 person years for patients with a pathogenic mutation and 1 per 10.8 person years for those with a variant of uncertain significance. No relapses were recorded in 67.3 person years off eculizumab in those with no rare genetic variants. Eculizumab was restarted in 6 individuals with functioning kidneys in whom it had been stopped, with no individual progressing to ESKD. We demonstrated that biallelic pathogenic mutations in RNA-processing genes, including EXOSC3, encoding an essential part of the RNA exosome, cause eculizumab nonresponsive aHUS. Recessive HSD11B2 mutations causing apparent mineralocorticoid excess may also present with thrombotic microangiopathy.

Risk Selection and Care Fragmentation at Medicare Accountable Care Organizations for Patients With Dementia.

Patients with dementia are a growing and vulnerable population within Medicare. Accountable care organizations (ACOs) are becoming Medicare's dominant care model, but ACO enrollment and care patterns for patients with dementia are unknown. The aim of this study was to compare differences in ACO enrollment for patients with versus without dementia, and in risk profiles and ambulatory care among patients with dementia by ACO enrollment status. Cohort study assessing the relationships between patient dementia, following-year ACO enrollment, and ambulatory care patterns. A total of 13,362 (weighted: 45, 499,049) person-years for patients [2761 (weighted: 6,312,304) for dementia patients] ages 65 years and above in the 2015-2019 Medicare Current Beneficiary Survey. We assessed differences in ACO enrollment rates for patients with versus without dementia, and in dementia-relevant ambulatory care visit rates and validated care fragmentation indices among patients with dementia by ACO enrollment status. Patients with versus without dementia were less likely to be enrolled in (38.3% vs. 44.6%, P<0.001), and more likely to exit (21.1% vs. 13.7%, P<0.01) ACOs. Among patients with dementia, those enrolled versus not enrolled in ACOs had a more favorable social and health risk profile on 6 of 16 measures (P<0.05). There were no differences in rates of dementia-relevant, primary, or specialty care visits. ACO enrollment was associated with 45.7% higher wellness visit rates (P<0.001), and 13.4% more fragmented primary care (P<0.01) spread across 8.7% more distinct physicians (P<0.05). Medicare ACOs are less likely to enroll and retain patients with dementia than other patients and provide more fragmented primary care without providing additional dementia-relevant ambulatory care visits.

Increased Risk of Glaucoma in Patients with Rosacea: A Nationwide Population-Based Cohort Study.

Rosacea is a chronic inflammatory skin disorder associated with various ocular manifestations. However, little is known about the association between rosacea and glaucoma. This study aimed to determine the risk of glaucoma in patients with rosacea. This nationwide population-based retrospective cohort study enrolled 1056 individuals with rosacea and 10,440 age- and sex-matched controls without rosacea from the Korean National Health Insurance System (NHIS) database from 2002 to 2015. The incidence rate of glaucoma was 1215.4 per 100,000 person-years (PYs) in patients with rosacea and 741.3 per 100,000 PYs in patients without rosacea. A significantly higher cumulative incidence probability of glaucoma was observed in patients with rosacea than in non-rosacea controls (p = 0.0004). Rosacea was associated with an increased risk of developing glaucoma (adjusted hazard ratio [aHR], 1.659; 95% confidence interval [CI], 1.245-2.211) compared to those without rosacea. In subgroup analysis, increased risk of glaucoma was observed in patients with rosacea younger than 50 years (aHR, 1.943; 95% CI, 1.305-2.893), females (aHR, 1.871; 95% CI, 1.324-2.644), and patients with hypertension (aHR, 1.561; 95% CI, 1.037-2.351) compared to those without rosacea. Rosacea is associated with an increased risk of developing glaucoma. Proper screening for glaucoma should be conducted in rosacea patients younger than 50 years, females, and patients with hypertension to better control the disease and prevent vision loss from glaucoma.

Risk of Psychiatric Disorders in Juvenile Idiopathic Arthritis: Population‐ and Sibling‐Controlled Cohort and Cross‐Sectional Analyses

The objective of this study was to examine the incidence and accumulated burden of psychiatric disorders in juvenile idiopathic arthritis (JIA) relative to the general population (GP) and to their same-sex siblings. We performed an observational register-based study from July 1, 2006, to December 31, 2020, with three different study population contrasts: 1) patients with incident JIA versus five age- and sex-matched GP individuals (cohort), 2) patients with incident JIA versus full same-sex siblings (cohort), and 3) patients with prevalent JIA at age 18 versus matched GP individuals (cross-sectional). We investigated six groups of psychiatric disorders defined via International Classification of Diseases, Tenth Revision codes: mood and anxiety, suicidal behavior, eating, sleeping, substance use, psychotic, plus an overall combined outcome (ie, at least one of the six). Incidences rates were compared through Cox regression (contrasts 1 and 2) and logistic regression (contrast 3), all adjusted for demographics, comorbidities, and proxies for socioeconomic status. During 25,141 person-years of follow-up of 4939 incident patients with JIA, the incidence of the overall combined outcome was 20.1 per 1000 person-years in patients with JIA versus 13.1 per 1000 person-years in the GP (adjusted hazard ratio [HR]=1.49 [95% confidence interval: 1.35-1.65]). The three most elevated HRs were obtained for sleeping disorder (1.91 [1.41-2.59]), suicidal behavior (1.60 [1.23-2.07]), and mood and anxiety disorders (1.46 [1.30-1.64]). The comparison of patients with JIA (n=1815) with their siblings (n=2050) for the overall combined outcome resulted in a nonstatistically significant HR (1.16 [0.82-1.64]). By age 18, patients with JIA were more likely to have been diagnosed with any psychiatric disorder (adjusted odds ratio=1.37 [1.25-1.50]). There is an increased burden of psychiatric morbidity in JIA, which holds both individual and familial components.

Increased Risk of Dementia in Patients with Atopic Dermatitis: A Nationwide Population-Based Cohort Study

Atopic dermatitis (AD) is a chronic inflammatory skin disorder with bimodal incidence peaks in early childhood and middle-aged and older adults. Few studies have focused on the risk of dementia in AD. The aims of this study were to analyse the incidence, and risk factors for dementia in patients with AD. This nationwide population-based retrospective cohort study enrolled 38,391 adults ≥ 40 years of age with AD and 2,643,602 controls without AD from the Korean National Health Insurance System (NHIS) database from 2009 to 2016. The cumulative incidence probability of all-cause dementia, Alzheimer's disease, or vascular dementia at 8 years was 50, 39, and 7 per 1,000 person-years in patients with AD, respectively. The adjusted risks of all-cause dementia (hazard ratio (HR), 1.072; 95% confidence interval (95% CI) 1.026-1.120), and Alzheimer's disease (HR 1.051; 95% CI 1.000-1.104) were increased in patients with AD. The effect of AD on the development of all-cause dementia and Alzheimer's dementia varied according to age and diabetes mellitus (all p for interaction, < 0.05). The risks of all-cause dementia and Alzheimer's disease were increased in patients with AD. Management of modifiable risk factors is important for preventing dementia in patients with AD.

Shortages of antiseizure medications in Australia and the association with patient switching, and adherence in a community setting

PurposeTo quantify sponsor-reported shortages of oral antiseizure medications in Australia, estimate the number of patients impacted, and the association between shortages and brand or formulation switching, and changes in adherence. MethodsA retrospective cohort study of sponsor-reported shortages (defined as where the supply of a medicine will not or will not be likely to meet the demand over a 6-month period) of antiseizure medications reported to the Medicine Shortages Reports Database (Therapeutic Goods Administration, Australia); cross-referencing shortages to the IQVIA-NostraData Dispensing Data (LRx) database, a deidentified, population-level dataset collecting longitudinal dispensation data on individual patients from ∼75% of Australian community pharmacy scripts. ResultsNinety-seven sponsor-reported ASM shortages were identified between 2019 and 2020; of those, 90 (93%) were shortages of generic ASM brands. Of 1,247,787 patients dispensed ≥1 ASMs, 242,947 (19.5%) were impacted by shortages. Sponsor-reported shortages occurred more frequently before the COVID-19 pandemic versus during the pandemic, however, shortages were estimated to affect more patients during the pandemic than before the pandemic. An estimated 330,872 patient-level shortage events were observed, and 98.5% were associated with shortages of generic ASM brands. Shortages occurred at a rate of 41.06 shortages per 100 person-years in patients on generic ASM brands versus 0.83 shortages per 100 person-years in patients on originator ASM brands. In patients taking a formulation of levetiracetam affected by a shortage, 67.6% switched to a different levetiracetam brand or formulation during shortages compared with 46.6% in non-shortage periods. ConclusionsApproximately 20% of patients on ASMs were estimated to have been impacted by an ASM shortage in Australia. The rate of patient-level shortages was approximately 50 times higher for patients on generic ASM brands versus originator brands. Shortages of levetiracetam were associated with formulation and brand switching. Improved supply chain management amongst sponsors of generic ASMs is needed to maintain the continuity of supply in Australia.

A235 “WHAT’S SPRUE WITH YOU?”: OLMESARTAN-INDUCED ENTEROPATHY AS AN UNCOMMON MIMICKER OF CELIAC DISEASE

Abstract Background Olmesartan-induced enteropathy is an uncommon mimicker of celiac disease. Symptoms include diarrhea and weight loss and pathology shows villous atrophy, intraepithelial lymphocytes, and subepithelial collagen deposition. In contrast to celiac disease, tissue transglutaminase (TTG) is not elevated and gluten avoidance does not induce clinical or histologic improvement. Both clinical and histologic findings are reversible with cessation of pharmacologic therapy. Purpose To raise clinician awareness of an uncommon but reversible cause of enteropathy. Method A 67-year old man presented with 3 months of progressive diarrhea and 35lb weight loss on a background of hypertension, dyslipidemia, and type 2 diabetes. His medications included olmesartan, amlodipine, metformin, aspirin, and atorvastatin, none of which were new. Infectious stool studies, serum and fecal inflammatory markers, imaging, TTG and IgA were normal. Panendoscopy revealed duodenitis with biopsies consistent with active enteritis, intraepithelial lymphocytosis and villous shortening suggestive of olmesartan-induced enteropathy given negative TTG. Olmesartan was discontinued. Result(s) His symptoms completely resolved over several weeks after discontinuation. Conclusion(s) Olmesartan is an uncommon but reversible mimicker of celiac disease. It was first described in 2012 in a case series of 22 patients, all of whom had negative celiac serology and demonstrated histologic and clinical improvement with cessation of olmesartan. Time from medication initiation to onset of symptoms ranged from 6 months to 7 years, with a mean of 3.1 years. While case reports exist of angiotensin-receptor blockers as causative agents, the most common is olmesartan, implicated in 94% of ARB-induced enteropathy cases in a recent systematic review. The exact mechanism of injury is unknown. The delay in onset of symptoms suggests a cell-mediated immunity phenomenon. An immune-mediated reaction is also supported by the high prevalence of HLA-DQ2/DQ8 haplotypes (71%) among affected individuals vs. 30-40% in the general population. Olmesartan may be implicated more strongly than other ARBs due to its higher affinity for AT1 receptors; theoretically leaving unsaturated AT2 receptors to bind angiotensin. AT2 receptors are known to induce cellular apoptosis, and unopposed cellular death could theoretically lead to villous atrophy. The overall risk of developing enteropathy on olmesartan is rare, but not well quantified. This is likely due to both underrecognition, and variability in study designs leading to inability to perform meta-analysis on currently available data. Data from a French cohort estimates a crude incidence rate of 5.6 per 100,000 person years for patients on olmesartan developing intestinal malabsorption requiring hospitalization. Despite its rarity, prescribers should be cognizant of this side effect which can evolve even after years of medical therapy. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

Systemic Lupus Erythematosus and Risk of Dry Eye Disease and Corneal Surface Damage: A Population-Based Cohort Study.

Systemic lupus erythematosus (SLE) potentially involves multiple parts of the ocular system, including the lacrimal glands and the cornea. The present study sought to assess the risk of aqueous-deficient dry eye disease (DED) and corneal surface damage in patients with SLE. We conducted a population-based cohort study using Taiwan's National Health Insurance research database to compare the risks of DED and corneal surface damage between subjects with and without SLE. Proportional hazard regression analyses were used to calculate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for the study outcomes. The propensity score matching procedure generated 5083 matched pairs with 78,817 person-years of follow-up for analyses. The incidence of DED was 31.90 and 7.66 per 1000 person-years in patients with and without SLE, respectively. After adjusting for covariates, SLE was significantly associated with DED (aHR: 3.30, 95% CI: 2.88-3.78, p < 0.0001) and secondary Sjögren's syndrome (aHR: 9.03, 95% CI: 6.86-11.88, p < 0.0001). Subgroup analyses demonstrated that the increased risk of DED was augmented among patients with age < 65 years and female sex. In addition, patients with SLE had a higher risk of corneal surface damage (aHR: 1.81, 95% CI: 1.35-2.41, p < 0.0001) compared to control subjects, including recurrent corneal erosion (aHR: 2.98, 95% CI: 1.63-5.46, p = 0.0004) and corneal scar (aHR: 2.23, 95% CI: 1.08-4.61, p = 0.0302). In this 12-year nationwide cohort study, we found that SLE was associated with increased risks of DED and corneal surface damage. Regular ophthalmology surveillance should be considered to prevent sight-threatening sequelae among patients with SLE.

WITHDRAWN: Evidence Synthesis to Advance Clinical Practice and Scientific Research: A CGH Pillar

WITHDRAWN: Evidence Synthesis to Advance Clinical Practice and Scientific Research: A CGH Pillar

Reconstructive types effect the prognosis of patients with tumors in the central and nipple portion of breast cancer? An analysis based on SEER database.

The impact of different types of reconstruction, including tissue reconstruction, implant reconstruction and combined reconstruction, on patient survival were not illustrated completely. We tried to investigate the impact of patient survival between different types of reconstruction. We enrolled 6271 patients with tumors in the central and nipple portion of breast cancer from the Surveillance, Epidemiology, and End Results database. Factors associated with survival were identified by Cox regression analyses. The mortality rates per 1,000 person-years were calculated and compared. Survival curves were produced by Kaplan-Meier analyses using log-rank tests and cox proportional hazards regression quantified the risk of survival. Reconstructive types, region, insurance, race, marial status, grade, stage, ER status, PR status, HER-2 status and chemotherapy were significant prognostic factors associated with breast cancer-specific survival. The breast cancer mortality rates per 1,000 person-years for patients with tissue, implant and combined group were 26.01,21.54 and 19.83 which showed a downward trend. The HR of implant and combined reconstruction adjusted for demographic, pathological, and therapeutic data was 0.82 (95% CI: 0.67-1.00, p=0.052) and 0.73(95% CI:0.55-0.97, p=0.03) compared with tissue reconstruction. Breast cancer-related mortality between implant reconstruction and autologous tissue reconstruction showed no significantly different, but the risk of BCSS of compound reconstruction was lower than tissue reconstruction.

A Systematic Review on the Association between Schizophrenia and Bipolar Disorder with Chronic Obstructive Pulmonary Disease

A systematic review aimed to investigate the association between schizophrenia and bipolar disorder and chronic obstructive pulmonary disease (COPD), its prevalence and incidence, potential factors associated with its occurrence and its impact on mortality among these patients. We performed the literature search in PubMed, Scopus and PsycInfo from inception to February 2022 and identified 19 studies: ten cross-sectional, 5 that included cross-sectional and longitudinal analyses, and 4 retrospective cohort studies. The reported prevalence of COPD ranged from 2.6% to 52.7% in patients with schizophrenia and between 3.0% and 12.9% in patients with bipolar disorder. Two studies reported an annual incidence of COPD of 2.21 cases/100 person-years in patients with schizophrenia and 2.03 cases/100 person-years in patients with bipolar disorder. Among the risk factors evaluated in three studies, only advanced age was consistently associated with the presence/occurrence of COPD in patients with schizophrenia and bipolar disorder; the role of tobacco consumption was not investigated in those three studies. According to two studies, the likelihood of mortality from COPD showed an over 3-fold increase in patients with schizophrenia and a 2-fold increase in those with bipolar disorder compared to the overall population; COPD was also associated with increased inpatient mortality. Available data indicate that COPD in patients with schizophrenia and bipolar disorder is a major public health problem. National and international health organizations should strive to specifically address this issue by creating awareness about this health problem and developing specific programs for screening and early intervention aimed to reduce the burden of COPD in these populations.

Rheumatoid Arthritis Associated with Dry Eye Disease and Corneal Surface Damage: A Nationwide Matched Cohort Study.

Rheumatoid arthritis is potentially connected to ocular disorders, such as corneal inflammation and lacrimal gland destruction. This study aimed to evaluate the risk of dry eye disease (DED) and corneal surface damage among patients with rheumatoid arthritis. In a nationwide cohort study, we utilized Taiwan’s National Health Insurance research database and conducted propensity score matching to compare the risks of DED and corneal surface damage between patients with and without rheumatoid arthritis. Proportional hazards regression analyses were used to calculate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for the outcomes of interest. The matching procedure generated 33,398 matched pairs with 501,377 person-years of follow-up for analyses. The incidence of DED was 23.14 and 10.25 per 1000 person-years in patients with and without rheumatoid arthritis, respectively. After adjusting for covariates, rheumatoid arthritis was significantly associated with DED (aHR: 2.03, 95% CI: 1.93−2.13, p < 0.0001). The association was generally consistent across the subgroups of age, sex, use of systemic corticosteroids, and different comorbidity levels. In addition, patients with rheumatoid arthritis had a higher risk of corneal surface damage (aHR: 1.36, 95% CI: 1.21−1.51, p < 0.0001) compared to control subjects. Other independent factors for corneal surface damage were age and sleeping disorders. Rheumatoid arthritis was associated with an increased risk of DED and corneal surface damage. Ophthalmological surveillance is required to prevent vision-threatening complications in this susceptible population.

Role of sodium-glucose cotransporter-2 inhibitors in risk of chronic kidney disease among patients with type 2 diabetes mellitus.

This retrospective analysis aims to explore the risk of chronic kidney disease (CKD) among type 2 diabetes mellitus (DM) patients with different scores of adapted diabetes complications severity index (DCSI) who received sodium-glucose cotransporter-2 inhibitors (SGLT2Is). This study includes 113,449 DM patients from the Taiwan National Health Insurance Research Database (NHIRD). We analyzed the data collected from 107,440 patients showing a DCSI score change of < 1 per year, 3720 patients with a score change of 1 to 2 per year and 2289 patients with a score change of > 2 per year. Cox proportional hazard models were used to evaluate the CKD risk throughout the overall follow-up period, and were adjusted for sex, age, comorbidities and medications of a-glucosidase inhibitors, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, biguanides, dipeptidyl peptidase-4inhibitors, glucagon like peptide-1 receptor agonists, insulin, meglitinides, sulphonylurea and thiazolidinedione. The incidence of CKD increased from 18.30 per 1000 person-years in patients with a score change of<1 per year to 137.55 per 1000 person-years for those with a score change of > 2 per year. Patients with a higher score change (> 2 per year) and receiving SGLT2Is had a lower risk of developing CKD than patients who did not receive SGLT2Is. The use of SGLT2Is was significantly associated with the reduction in CKD incidence in diabetic patients with a higher DCSI.

The Association between Infectious Mononucleosis and Cancer: A Cohort Study of 24,190 Outpatients in Germany.

Background: Cancer represents one of the leading causes of death worldwide. Besides genetic risk factors and non-communicable diseases, chronic infections including Epstein−Barr virus (EBV) infection have been identified as promotors of cancer. In the present manuscript, we evaluated the association between infectious mononucleosis, the clinical manifestation of EBV infection, and cancer development in a real-word cohort of outpatients in Germany. Methods: We used the Disease Analyzer database (IQVIA) and matched a total of 12,095 patients with infectious mononucleosis to a cohort of individuals without infectious mononucleosis based on age, sex, index year, and annual patient consultation frequency between 2000 and 2018. Results: Patients diagnosed with infectious mononucleosis had a cancer incidence of 5.3 cases per 1000 person years versus 4.4 cases per 1000 person years for patients without infectious mononucleosis. In multivariable regression models, infectious mononucleosis showed a trend towards a higher incidence of cancer in general in the age group > 50 years (incidence rate ratio (IRR): 1.32; 95% CI: 1.04−1.67) and among men (IRR: 1.36; 95% CI: 1.07−1.72). Infectious mononucleosis was significantly associated with an increased incidence of tumors of the hematopoietic and lymphoid tissues (IRR: 1.75; 95% CI: 1.22−2.50) and showed a strong trend towards an association with prostate cancer (IRR: 3.09; 95% CI: 1.23−7.76). Conclusion: Infectious mononucleosis is associated with an increased incidence of certain cancer types. The present data from a large real-world cohort support the evidence on a role of EBV in the development of different malignancies and could trigger research efforts to further elucidate its precise involvement in the carcinogenic process.

High Incidence of Herpes Zoster in Patients Using Ruxolitinib for Myeloproliferative Neoplasms: Need for Prophylaxis.

High Incidence of Herpes Zoster in Patients Using Ruxolitinib for Myeloproliferative Neoplasms: Need for Prophylaxis.

Predictive model for autonomous cortisol secretion development in non-functioning adrenal incidentalomas.

We aimed to develop a predictive model able to stratify patients with non-functioning adrenal incidentalomas (AIs), according to their risk for developing autonomous cortisol secretion (ACS) during follow-up. This was a retrospective study of patients with non-functioning AIs consecutively evaluated at a single institution between 2013 and 2019 in whom hormonal follow-up information was available for at least 1year. Clinical, biochemical, and radiological features were used to build a multivariate Cox regression model using the estimation of all possible equations. We included 331 patients with non-functioning AIs. ACS (post-dexamethasone suppression test (DST) serum cortisol > 1.8µg/dL) developed in 73 patients during a median follow-up time of 35.7months [range 12.8-165.4]. The best predictive model for ACS development during follow-up combined age, post-DST serum cortisol, and bilaterality at presentation and showed good diagnostic accuracy (AUC-ROC 0.70 [95% CI 0.65-0.75]). The lowest risk for ACS development was found among patients < 50years old with cortisol post-DST values < 0.45µg/dL and with unilateral tumors (risk 2.42%). Baseline post-DST serum cortisol levels at diagnosis were the most important factor for the development of ACS during follow-up (hazard ratio 3.56 for each µg/dL, p < 0.001). The rate of ACS development was associated with post-DST cortisol levels, being 19.2, 32.3, and 68.1 cases/10,000 person-years for patients with baseline post-DST cortisol < 0.9µg/dL, 0.9-1.3µg/dL, and > 1.3µg/dL, respectively. After ruling out malignancy, follow-up visits for patients < 50years old with unilateral non-functioning AIs and post-DST serum cortisol < 0.45µg/dL are considered unnecessary given the low risk of developing ACS during follow-up.

Outcome of sedentary patients: does the power of zero cac make a difference?

Abstract Introduction Coronary artery calcium score (CACS) and exercise capacity (EC) are both independent prognostic tests in coronary artery disease (CAD). Purpose We aimed to assess the incremental prognostic role of EC to CACS, particularly in those with absent or low coronary calcification. Methods The cohort consisted of patients who had clinically indicated exercise stress testing and CACS assessment with a median of 27 days of each other. EC was defined based on peak metabolic equivalents (METS) achieved during exercise stress test. CACS was determined using the Agatston method. Patients were followed from the latest test date to incident MACE (inclusive of all-cause death, non-fatal myocardial infarction, late revascularization and admission for heart failure). Results There were a total of 1932 patients in the study population (mean age 56±12, 42% female, 48% hypertension, 21% diabetes, 48% dyslipidemia). Peak METS &amp;lt;6 was achieved in 8% of patients, and the median (IQR) CACS was 9 (0–203). Patients with EC &amp;lt;6 METS had doubling of their event rate across strata of CACS, even amongst patients with absent or low coronary calcifications (CACS 0: 4.6 vs 10.9; CACS 1–99: 10.4 vs 20.4; MACE per 1000 person year in patients with peak METS ≥ vs &amp;lt;6 respectively) (Figure 1). Conclusion Our findings showed that poor exercise capacity was associated with higher risk even in patients with absent or low coronary calcification. Funding Acknowledgement Type of funding sources: None.

The impact of mitral regurgitation on the incidence of stroke in patients with atrial fibrillation

Abstract Background Stroke is a significant cause of mortality and a leading cause of disability in elderly patients. Atrial fibrillation (Af) is the most common cardiac disease with assumed embolic stroke. Therefore, patients with Af need anti-coagulant therapy with a Warfarin (vitamin K antagonist) or a DOAC (Direct Oral Anti-Coagulant), also considering the risk and benefit net balance. It has been suggested that significant mitral regurgitation (MR) and its vortex jet in the left atrium might reduce embolic stroke source in patients with Af. However, the effect of MR on the risk of stroke in patients with Af is still controversial. Therefore, we hypothesized whether MR might be associated with a lower risk of thromboembolic events in patients with Af. Purpose This study aims to investigate whether MR was associated with a decreased risk of stroke in patients with Af, especially in the elderly population. Methods We studied 1,714,955 patients in the LIFE Study database, comprising Japanese claims data for public insurance policyholders between 2014 and 2020. We identified 51,939 patients with new-onset Af. Among them, patients with pre-existing stroke patients (N=28,519) were excluded, and new-onset Af patients without stroke (N=23,420) were obtained. Based on the baseline information, the Af patients were stratified into the MR group (N=3,439) and Without-MR group (N=19,981). Propensity score matching (the nearest neighbor method with a caliper of 0.2) was performed to balance baseline features and stroke risk factors between the MR group (N=3439) and the Without-MR group (N=3439). Propensity scores were estimated using logistic regression with age, sex, and all factors in Elixhauser's comorbidity system. The incidence rate of the stroke (events per person-year) was calculated by the event numbers divided by the overall period for the observations months × 12. Kaplan-Meier curves of stroke-free survival were generated, and the two groups' comparisons were performed using the log-rank test. Results As expected, patients' characteristics were comparable between the two groups. The observation period was 3 years for both groups. In the MR group, 136 patients with stroke were detected. On the other hand, 122 patients with stroke were detected in the Without-MR group. The incidence rate of the stroke per person-year was 0.027 and 0.025 events per person-year in patients with the MR and Without-MR groups. In addition, the Kaplan-Meier analysis showed that the incidence rate of stroke was comparable between the two groups (P=0.43). Conclusions The frequency of stroke in patients with atrial fibrillation was similar, despite mitral regurgitation. Therefore, patients with atrial fibrillation should have anti-coagulation therapy, regardless of the presence or absence of mitral regurgitation. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): This work was supported by grants provided by the Japan Science and Technology Agency (JST) Fusion Oriented Research for disruptive Science and Technology (FOREST) Program (Grant Number: JPMJFR205J) and the Japan Society for the Promotion of Science (JSPS) Grants-in-Aid for Scientific Research (KAKENHI) Program (Grant Numbers: JP20H00563 and JP19K21590).

Heart failure and long-term prognosis in patients with congenital heart disease: a nationwide, register-based cohort study

Abstract Introduction Heart failure (HF) is associated with high morbidity and severe prognosis. The aim of this study was to investigate the risk of HF in patients with congenital heart disease (CHD) and to determine the prognosis after HF diagnoses in patients with CHD compared to HF controls without CHD. Methods We identified 89,532 patients with CHD born between 1930 and 2017 from the National Patient Register in Sweden and matched with 10 controls without CHD by gender and birth year from the National Population Register. The study population was followed-up until 2017, through the Swedish Patient Register and Cause of Death Register. Results Altogether, 7,013 (7.8%) patients with CHD and 9,681 (1.1%) controls developed HF. The overall incidence rate of HF was 31.6 per 104 person-years in patients with CHD and 4.0 per 104 person-years in controls. The mean age for HF diagnoses was 40.3 (± 28.8) in patients with CHD and 66.4 (± 13.6) for controls. The risk for developing HF was significantly higher in complex than non-complex CHD lesion groups, HR 28.7 (26.5–31.0) and HR 6.9 (6.7–7.2) respectively. Mortality incidence rate was twice as high in controls with HF compared to CHD with HF (IR 9.7 (9.4–10.0) and 4.74 (4.6–4.9), respectively). The mortality incidence was higher within all age groups except for 18–39 years and there was no difference between complex and non complex lesions Conclusion One out of thirteen CHD patients will develop HF. The highest risk for HF is within CHD patients with complex lesions. CHD patients develops HF at a considerably younger age, reflecting their slightly better prognosis after development of HF compared to controls with HF. Funding Acknowledgement Type of funding sources: None.

Risk of Juvenile Idiopathic Arthritis and Rheumatoid Arthritis in Patients With Celiac Disease: A Population-Based Cohort Study.

Celiac disease (CD) is associated with many immune-mediated conditions, but a definitive epidemiological association between CD and juvenile idiopathic arthritis (JIA) or rheumatoid arthritis (RA) has not been established. We quantified the risk of JIA and RA among patients with CD using a population-based cohort. We identified patients diagnosed with biopsy-proven CD between 2004 and 2017 using data from a national histopathology cohort in Sweden. Each patient was matched by age, sex, calendar year, and geographic region to reference individuals in the general population. We calculated the incidence and estimated the relative risk, through Cox proportional hazards models, of JIA in individuals with CD aged <18 and of RA in individuals with CD aged ≥18. We identified 24,014 individuals with CD who were matched to 117,397 reference individuals from the general population. Among individuals aged <18, the incidence rate of JIA was 5.9 per 10,000 person-years in patients with CD and 2.2 per 10,000 person-years in the general population (n events = 40 and 73, respectively; hazard ratio [HR] 2.68, 95% confidence interval 1.82-3.95) over a follow-up of 7.0 years. Among individuals aged ≥ 18, the incidence of RA was 8.4 per 10,000 person-years in CD and 5.1 per 10,000 person-years in matched comparators (n events = 110 and 322, respectively; HR 1.70, 95% confidence interval 1.36-2.12) over a follow-up of 8.8 years. Among children with CD, JIA develops nearly 3 times as often as it does in the general population, and among adults with CD, RA occurs nearly 2 times as often. Clinicians caring for patients with CD with joint symptoms should have a low threshold to evaluate for JIA or RA.