Date Of Diagnosis Research Articles

HPB SO48 - Evaluating the timeframe for the provision of laparoscopic cholecystectomy in acute cholecystitis patients at a regional hospital

Abstract Background Acute biliary disease comprised a substantial proportion of the general emergency surgical workload. AUGIS and NICE guidelines recommend early laparoscopic cholecystectomy (LC) in acute cholecystitis (AC) patients as it is associated with reduced readmission rates, healthcare costs and faster recovery without notable complication risks. According to the local trust policy, it advocates early LC to be performed within 72 hours of admission for AC patients. If this is not possible a delayed LC should be performed within 8 weeks of admission. Our aim is to examine variations in the provision of LC between current practice and local trust/ NICE guidelines. Method This is a retrospective audit looking at the total number of surgical patients diagnosed with AC between Jan and Dec 2023. The number of patients who had LC in 2023, unfit for surgery and did not consent for the procedure were also included. This data was obtained from electronic patient records (investigative reports, discharge letters, outpatient letters) and then collated on a Microsoft Excel sheet for analysis. Surgical patients who were not diagnosed with AC such as those with biliary pancreatitis, cholelithiasis or cholangitis but subsequently underwent LC were excluded. Results The number of AC patients who were fit and consented to surgical intervention in 2023 was 88. The total number of delayed procedures done was 75 (85.2%). The number of patients who had early LC within 1 week was 13 (14.8%). Of the 75 patients who had delayed LC, 19 (25.3%) patients had delayed LC within 8 weeks from the diagnosis date. The remaining 56 (74.7%) patients had delayed LC after 8 weeks. For patients who had delayed LC, the readmission rate within 6 months of their discharge while waiting for their operative dates was 29 (38.7%). Conclusion One-third of AC patients were readmitted while waiting for LC, some had complications of gallstone disease such as perforation/ gallstone ileus. Therefore, the early provision of LC is crucial in minimising the readmission and complication rates. This data was highlighted in a departmental meeting and teaching session for consultants and junior doctors. We plan to liaise with stakeholders and theatre managers in implementing further solutions to improve compliance where possible. One critical area is auditing the condition of surgical patients in order to be put on the hospital’s twice-weekly hot gallbladder list to consider prioritising AC patient surgical time.

Abstract 4138220: Traditional and HIV-specific Risk Factors Are Associated with Incident Non-valvular Atrial Fibrillation and Atrial Flutter among Underrepresented Racial and Ethnic Minority Groups Living with HIV

Introduction: With effective antiretroviral therapy (ART), HIV can now be managed as a chronic disease. Chronic disease and cardiovascular risk factor management is especially important for underrepresented racial and ethnic minority groups (UREG). Non-valvular atrial fibrillation and atrial flutter (NVAF) have not been adequately studied in UREG with HIV. Research Questions: Among UREG with HIV, what is the incidence of NVAF? What factors are associated with incident NVAF? Aims: To narrow an evidence gap among UREG with HIV by 1) describing the incidence of NVAF and 2) identifying factors associated with incident NVAF. Methods: This is an ancillary study of the Pathways to Cardiovascular Disease Prevention and Impact of Specialty Referral in Underrepresented Racial and Ethnic Minorities with HIV (PATHWAYS) study, a retrospective population-based study of HIV care patterns among UREG with HIV. Patients without a known history of NVAF entered our study cohort at the date of their first documented HIV diagnosis. We computed the cumulative incidence of NVAF over five years of follow-up (mean 3.4, SD 1.6), handling death as a competing risk. Cox regression analysis was used to examine the univariate associations between characteristics at HIV diagnosis and incident NVAF, adjusting for site and date of HIV diagnosis. Results: From 2015-2019, 10,945 UREG meeting entry criteria were identified. On average, patients were 67.1% male, 94.4% Black, and 8.5% Hispanic. Average CHA2DS2VASc score was 0.92 (SD 1.1) and 63.4% were on ART. Cumulative incidence of NVAF at one and five years after HIV diagnosis were 0.48% (95% CI 0.36-0.63) and 2.16% (95% CI 1.85-2.51), respectively. HIV-related factors associated with incident NVAF included baseline CD4 count <200 (HR 1.84, 95% CI 1.20-2.80) and initial ART including protease inhibitors (HR 1.56, 95% CI 1.14-2.13) and/or integrase strand transfer inhibitors (HR 1.47, 95% CI 1.08-1.99). Additional associated factors included older age, Medicare, cardiology visit(s) in prior year, and co-morbid diseases including hypertension, hyperlipidemia, coronary and peripheral artery disease, prior stroke/transient ischemic attack, heart failure, and chronic kidney disease. Conclusions: In a large cohort of UREG living with HIV, both traditional and HIV-specific risk factors are associated with increased risk of incident NVAF. Interventions to mitigate NVAF risk in this population will require interdisciplinary, team-based approaches.

RADT-07. HYPOFRACTIONATED RADIOTHERAPY IN BRAINSTEM GLIOMAS- EXPERIENCE FROM A TERTIARY CARE CENTRE IN INDIA

Abstract Brainstem Gliomas have limited therapeutic options and poor outcomes. Radiation forms the cornerstone of management but data is lacking. We performed an audit of brainstem glioma patients treated with hypofractionated radiation between July 2021 to May 2024. Diagnostic MRI was co-registered with planning CT to delineate GTV with an isotropic 5 mm margin for CTV and 3mm for PTV. Baseline clinical and imaging details, radiation details, acute toxicities, steroid usage, progression, and overall survival data were recorded. PFS and OS were defined from the date of diagnosis to progression and death respectively. This study included 31 Brainstem glioma patients. The median age at presentation was 14 years (2–80 years). Majority of patients were male (67.7%). The baseline performance status assessed by ECOG/Lansky was 0-2 in 83.9%. The most common presenting complaint was motor weakness in 51.6% followed by cerebellar symptoms in 29%. Baseline neurological deficit was seen in 90.3%. The most common epicenter of the disease was pons (67.7%). Biopsy was available in only 9.7% (2 patients: Diffuse Midline Glioma H3k27 altered,1: High-Grade Glioma). VP shunting was done in 29%. All patients were planned via VMAT technique. Median GTV volume 34.3cc (4.9-109.5cc). Median PTV volume was 95.1 cc (7.9-363.1 cc). Most frequently used regimen was 40Gy/15#/3 weeks in 74.3% of patients. Median PTV coverage D95% was 98.7% (90.5-99%). Only one patient received concurrent Temozolamide. Median Radiation treatment time was 22.5 days (-46 days). Steroid usage during radiation was seen in 41.9% of the patients. Naso-gastric tube was required in 12.9% patients. During radiation, aspiration and raised ICT were seen in in 12.9% each. At a median follow-up of 6.42 months, the median PFS was 6.42 months (3-9.83 months) and OS was 7.18 months (3-11.37 months). Hypofractionation seems a feasible approach in brainstem gliomas. International collaborative efforts are required.

NIMG-66. DEFINING PROGRESSIVE DISEASE: LOCALIZING VOXEL-AT-RISK ON MAGNETIC RESONANCE IMAGING USING DEEP LEARNING

Abstract Follow-up magnetic resonance imaging (MRI) of post-treatment glioblastoma (GBM) can be diagnostically challenging in differentiating progressive disease (PD) from coexisting treatment-related changes. The study aim was to train a machine learning model using multiple MRI timepoints from treated GBM patients with subsequent PD or at least six months of tumor-like, persistently stable disease (SD) to estimate PD risk. A retrospective, post-treatment GBM cohort (n=189) with 453 timepoints was identified with available MRI sequences (T1-weighted with and without contrast, T2-weighted, and fluid-attenuated inversion recovery). PD cases (n=154) showed new, enhancing PD followed by death within 3-6 months; timepoints included the MRI on the PD diagnosis date and the one directly prior. SD cases (n=35) exhibited stable, tumor-like enhancement over timepoints. Cases underwent voxel-wise annotation of PD versus SD. A multiclass, three-dimensional nnU-Net was trained to label voxels as PD, SD, or neither using timepoint sequences with five-fold cross-validation. Model performance was assessed using the ratio of predicted PD/SD voxels compared to each case’s actual PD or SD status. Classification accuracy of PD versus SD status, PD case-wise sensitivity and specificity, and a Receiver Operating Characteristic (ROC) analysis using the PD/SD ratio were presented. The five-fold model ensemble was evaluated on a holdout test set. Validation set performance showed 74.3% accuracy, 0.73 PD case-wise sensitivity, and 0.80 specificity. The holdout set exhibited 79.8% accuracy, 0.81 sensitivity, and 0.78 specificity for PD cases. The ROC analysis showed an area under the curve of 0.80 and 0.83 on the validation and holdout sets, respectively. The model showed high performance and classification accuracy in predicting which voxels were at risk of PD in post-treatment GBM cases. The model also differentiated between PD and SD regions. The model’s predicted PD/SD ratio may be clinically used to stratify patients’ PD risk.

EPID-30. THE COST OF HOSPITAL-BASED CARE AMONG CANADIAN PATIENTS WITH MALIGNANT CENTRAL NERVOUS SYSTEM TUMOURS IN COMPARISON TO THOSE WITH LUNG AND COLORECTAL CANCERS IN THE YEAR PRECEDING THEIR CANCER DIAGNOSIS

Abstract BACKGROUND Approximately 12% of the Canadian GDP was spent on healthcare in 2023. While hospital-based care (HC) constitutes a significant portion of this expenditure, the costs may vary depending on the cancer type. We investigate the HC cost of patients with malignant central nervous system tumours (CNS cancer) and compare it to patients with common cancers in Canadian provinces. METHODS We obtained data between 2010 and 2014 from the Canadian Institute for Health Information’s in-patient and ambulatory care datasets. HC cost was estimated using a 12-month look back period prior to diagnosis date for each patient, including cost related to cancer diagnosis and general healthcare. Choosing colorectal (CRC) and lung (LC) cancers to be the common cancers, patients who were 15 years of age or older and had a diagnosis of one of these cancers were included. We used quantile regression to investigate the factors associated with HC cost. RESULTS A total of 4,498 (CNS), 41,028 (CRC) and 29,747 (LC) patients were included from Alberta and Ontario, Canada. Encounter type (in-patient/out-patient), province (AB/ON), and comorbidities (Yes/No) were the top three factors contributing to HC cost. Adjusting for encounter type, comorbidities and age, the HC costs for CNS patients were $0.7k and $2.4k higher than CRC patients at 50th and 90th percentile, respectively, and $1.0k higher than LC patients at 90th percentile in Ontario. While in Alberta, HC costs for CNS patients were $0.2k and $0.8k higher than CRC patients at 50th and 90th percentile, respectively, and $1.0k lower than LC patients at both 50th and 90th percentiles. CONCLUSIONS We compared HC cost among Canadian patients with different cancer types; significant HC cost differences between patients with CNS and common cancer were observed. Further investigations are warranted to understand drivers of the cost differences.

The relationship between seasonality and the diagnosis of acute leukaemia in central South Africa

Background: Leukaemias are haematological malignancies resulting from the abnormal clonal proliferation of haematopoietic precursors. Their incidence is influenced by various environmental and genetic factors.Aim: With this retrospective descriptive study, the authors aimed to explore the possible influence of seasonality on the type and number of acute leukaemia (AL) diagnoses made at the Universitas Academic Hospital (UAH) National Health Laboratory Service (NHLS) from 01 January 2018 to 31 December 2021.Setting: Universitas Academic Hospital, Bloemfontein, South Africa.Methods: Archived laboratory reports of all patients diagnosed with lymphoid and myeloid during the study period were included. Patients’ age, sex, ethnicity, final diagnosis and date of diagnosis were recorded. Information was pseudonymised to maintain confidentiality. A descriptive statistical analysis was performed to explore the possible influence of seasonality on the number of cases and type of leukaemia diagnosed.Results: In all, 249 patients were included. Acute myeloid leukaemia (AML) was the most common AL subtype (n = 117; 47.0%). Over the 4-year study period, all AL subtypes were more frequently diagnosed in summer (n = 131; 52.6%). However, the monthly number of AL diagnoses was relatively consistent over the 4 years for all subtypes (p = 0.7603), with consistent peaks of AML cases during January and February (summer) and May (autumn).Conclusion: No statistically significant association between the different seasons and AL diagnosis was noted.Contribution: Further studies using a larger study population and a wider geographical area, conducted over a more extended period, might affect the observations made in this study

A Retrospective Claims Analysis of the Rate of Complications in Patients Undergoing Treatment for Paroxysmal Nocturnal Hemoglobinuria.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disease associated with complications that increase morbidity, such as thrombosis and chronic kidney disease. Limited data exist regarding complications among treated patients outside of clinical trials, especially for patients treated with ravulizumab. This study leverages MarketScan claims data to examine the rate of complications in patients receiving PNH treatment. Patients with a diagnosis code of PNH [International Statistical Classification of Diseases and Related Health Problems (ICD-10) diagnosis code: D59.5] between October 2015 and December 2020, aged≥18 on the date of diagnosis, who had a≥6-month follow-up period of continuous enrollment and≥1 PNH-indicated treatment on or after the first PNH diagnosis were included. Among 211 patients diagnosed with PNH being treated with eculizumab or ravulizumab between October 2015 and December 2020, the most common complications were iron deficiency (20.4% of patients), arterial embolism and thrombosis (16.1%), and chronic kidney disease (11.8%). Overall, 44.1% of patients experienced≥1 complication. The high number of patients with PNH receiving treatment who nevertheless experienced complications demonstrates significant unmet medical need. Further analysis with larger sample sizes and including newer therapies, such as pegcetacoplan and iptacopan, is required to fully understand the scope and magnitude of this unmet need.

Recurrence of Cardiovascular Events After an Acute Myocardial Infarction in Patients with Multivessel Disease and Associated Healthcare Costs: A German Claims Data Analysis.

This study sought to quantify the healthcare costs of multivessel disease (MVD) and determine the prevalence and incidence of recurrent major adverse cardiovascular events (MACE) in high-risk patients diagnosed with MVD following an acute myocardial infarction (MI). This retrospective study utilized German claims data (AOK PLUS), between 01/01/2010 and 31/12/2020. Patients were included if they (1) had an inpatient diagnosis of an MI between 01/01/2012 and 31/12/2019 (index date), (2) were ≥ 18 years of age at date of MI diagnosis, and (3) had diabetes or met two of the following criteria: ≥ 65 years old, prior MI, peripheral arterial disease. MACE was defined as (1) MI, (2) stroke, or (3) death with a cardiovascular diagnosis within 30 days prior. To measure the burden of MVD, patients were identified during the index hospitalization by presence of MVD. Healthcare resource use and costs were compared after adjustment based on propensity score matching (PSM). A total of 5158 patients with evidence for MVD were included in the main analysis. 31.17% experienced a MACE within 365 days following the incident MI. After PSM adjustment, 33.22% of the MVD cohort experienced a MACE versus 36.48% of non-MVD patients. MVD patients had a higher rate of recurrent MI (14.22% vs. 9.81%). Additionally, public healthcare costs were about €4 million higher in the total MVD cohort than in the non-MVD cohort in the first year after an MI (€47,896,012.32 vs. €43,718,713.75, respectively), reflecting the MVD cohort's higher use of the public healthcare system. More MVD patients were prescribed guideline-recommended medication (61.4% vs. 46.0%). This study found that presence of MVD contributed to higher rates of recurrent MI. Patients with MVD experienced higher rates of recurrent MI despite a higher proportion of patients receiving guideline-directed medication therapy compared to non-MVD patients. Conversely, there was a higher mortality rate observed in the non-MVD cohort.

Emergency department use before cancer diagnosis in Ontario, Canada: a population-based study.

Although suspicions of cancer may be raised in patients who visit the emergency department, little is known about emergency department use before a cancer diagnosis. We sought to describe emergency department use among patients in Ontario within the 90 days before confirmed cancer diagnosis and to evaluate factors associated with this emergency department use. We conducted a retrospective, population-based study of patients aged 18 years or older who had a confirmed cancer diagnosis in Ontario from 2014 to 2021 using linked administrative databases. The primary outcome was any emergency department visit within 90 days before the cancer diagnosis date. We used multivariable logistic regression to evaluate factors associated with emergency department use, such as demographics (e.g., age, sex, rurality, Ontario Health region, indicators of marginalization), comorbidities, previous emergency department visits and hospital admissions, continuity of primary care, type of cancer, and year of cancer diagnosis. We included 651 071 patients with cancer. Of these, 229 683 (35.3%) had an emergency department visit within 90 days before diagnosis, 51.4% of whom were admitted to hospital from the emergency department. Factors associated with increased odds of emergency department use before cancer diagnosis included rurality (odds ratio [OR] 1.15, 95% confidence interval [CI] 1.13-1.17), residence in northern Ontario (North East region OR 1.14, 95% CI 1.10-1.17 and North West region OR 1.27, 95% CI 1.21-1.32, v. Toronto region), and living in the most marginalized areas (material resources OR 1.37, 95% CI 1.35-1.40 and housing OR 1.09, 95% CI 1.06-1.11, v. least marginalized quintile). We observed significant variation in emergency department use by cancer type, with high odds of emergency department use among patients with intracranial, pancreatic, liver or gallbladder, or thoracic cancer. Emergency department use is common before cancer diagnosis, with about one-third of patients with cancer in Ontario using the emergency department before diagnosis. Understanding why patients visit the emergency department before cancer diagnosis is important, particularly for patients who live in rural or marginalized areas, or those who have specific cancer types.

Impact of Age and Gender on Survival of Glioblastoma Multiforme Patients: A Multicenter Retrospective Study.

Glioblastoma multiforme (GBM) poses a significant health challenge as the most common primary malignancy of the adult central nervous system. Gender- and age-related differences in GBM influence prognosis and treatment complexities. This multicenter retrospective study explores gender and age disparities in GBM patients, investigating their impact on occurrence and survival outcomes. This multicenter retrospective study involved GBM patients treated in Guilan Province, Iran. Patients' data, including age, gender, tumor location, and histopathological diagnosis date, was collected from medical records. In a cohort of 164 GBM patients, the average age was 54.34 ± 14.16 years, with a higher prevalence among men (59.8%) and patients aged ≤ 60 years (64.6%). The tumor sites exhibited overlapping features in 68% of cases, with the frontal and temporal lobes being the most common specific locations. The mean survival was 12.88 ± 14.14 months, one-year survival of 45%, with women showing significantly higher one-year survival (60% vs. 40%) and longer mean survival (16.14 ± 17.35 vs. 10.75 ± 11.15 months). Furthermore, Patients ≤ 60 years had significantly higher one-year survival (75% vs. 35%). In subgroup analysis, women had significantly higher survival rates in patients ≤ 60 years. However, among patients over 60, women exhibited a more pronounced decline in survival rates, with no statistically significant difference between men and women in this age group. This study highlights that both age and gender significantly affect GBM survival outcomes. Younger patients, particularly women, exhibited better survival rates, while older patients, especially women, showed poorer outcomes. These findings suggest the need to stratify treatment approaches by both age and gender to optimize care and improve survival in GBM patients. Further research is recommended to explore these associations.

Real-World Evaluation of Treatment Patterns, Healthcare Costs, and Healthcare Resource Utilization Among Patients with Non-small Cell Lung Cancer in the US Receiving Sotorasib.

Sotorasib was the first drug approved for adults with Kirsten rat sarcoma G12C-mutated locally advanced/metastatic non-small cell lung cancer (NSCLC) who received prior systemic therapy in the US. This study aimed to provide initial real-world evidence on patient characteristics, treatment patterns, healthcare resource utilization (HCRU), and healthcare costs (HCC) associated with sotorasib in US clinical practice. A retrospective observational study was conducted using the Optum Clinformatics® Data Mart US claims database spanning January 2016 to March 2023. The study population included adults with a diagnosis of lung cancer (diagnosis (Dx) date), claims for sotorasib on/post-Dx date (index date), Continuous enrollment for medical/pharmacy benefits from 180 days pre-Dx date to≥30 days post-index date was required. Patients receiving treatments for small-cell lung cancer (SCLC) pre-index were excluded. Outcomes were analyzed for patients receiving sotorasib as second or subsequent line (2L+) treatment and included adherence [proportion of days covered (PDC)], treatment duration, time to next treatment (TTNT), HCRU, and HCC during sotorasib treatment. Among 169 patients with lung cancer that met all inclusion criteria, 140 patients received sotorasib as 2L+ treatment (mean age: 71 years; 67.1% females). Mean PDC for sotorasib was 94.9%. Kaplan-Meier median treatment duration was 4.3 months. Median TTNT in patients with subsequent treatment (n=31) was 6.8 months. During sotorasib treatment, patients had a mean 3.87 outpatient, 0.09 inpatient, and 0.11 emergency visits per month. Mean monthly HCC during sotorasib treatment were US$23,063 versus $25,541 during the 180-day pre-index period. Patients in the US receiving sotorasib as 2L+ therapy for NSCLC in real-world clinical practice showed high adherence, TTNT comparable to progression-free survival observed in clinical trials, and HCC similar to those immediately prior to treatment demonstrating real-world benefits with no additional impact on healthcare resources with sotorasib.

Gout diagnoses uncertain when made by general practitioners without serum uric acid testing: an observational study.

General practitioners (GPs) diagnose the majority of all gout patients. They make their diagnosis clinically. Serum uric acid (SUA) level >0.35mmol/l is largely determinative for the clinical diagnosis of gout. We aimed to assess to what extent GPs test SUA when making a first gout diagnosis, and to consider consequences regarding diagnostic certainty of not testing it. We calculated proportions of patients from 87 Dutch general practices (1-1-2013 to 1-1-2022) with a first gout diagnosis and a recorded SUA test, evaluated if SUA testing was punctually timed with respect to the diagnosis date, whether SUA levels were >0.35mmol/L, and whether diagnoses corresponded with diagnoses according to the 'Acute Gout Diagnosis Rule' (AGD-rule). In 43.0% of 7782 patients (mean age 64.4 years; 68.8% male) no SUA test result was recorded, with substantial variation among practices: median 41.9% (IQR 20.2%). 'Gout very likely' according to the AGD-rule was seen in all males and in 83.1% of females when a punctually timed SUA >0.35mmol/L was present. When such SUA level was lacking, 'Questionable or indeterminate gout diagnosis' was seen in all males and in 67.1% of females, and 'Arthritis diagnosis other than gout' in 32.9% of females. GPs diagnosed gout without testing SUA in ~40% of cases. This implies avoidable diagnostic uncertainty with impact for the clinical care of many patients as well as for studies that include primary care patients with gout. Key Points • Serum uric acid (SUA) level > 0.35mmol is determinative when diagnosing gout: however, it is unknown how often SUA testing is applied as such. • More than 40% of patients with a first gout diagnosis according to general practitioners (GPs) had no SUA test result registered in their medical record. • Gout diagnosing by GPs without SUA testing appeared to lead to avoidable diagnostic uncertainty, as diagnoses are often questionable or sometimes even wrong. • Researchers investigating gout need to take into account diagnostic uncertainty if they include gout patients who are diagnosed in primary care in their studies without SUA information.

Incidence of cardiovascular diseases among breast cancer patients: a nationwide registry study 2013-2020

Abstract Background and aims There is evidence to suggest that breast cancer (BC) treatment is associated with an increased risk of developing cardiovascular disease (CVD). Several countries have introduced clinical measures to reduce the impact of breast cancer treatment on cardiovascular function including activated breathing control during radiotherapy, lower radiation doses, and maximum anthracycline doses. The overall aim of this study was therefore to investigate whether breast cancer patients still exhibit higher rates of cardiovascular disease than the general population. Methods We conducted a registry-based cohort study using linked data from four nationwide health registries. Out study population included all Norwegian patients diagnosed with BC between 2013-2020 and matched them by age to 10 controls without BC. Health outcomes were measured from 2008 to 2021. We estimated the cumulative incidence from index date, for ten selected CVDs. For BC patients, the index date was defined as date of BC diagnosis. For controls, the index date was defined as the date of BC diagnosis for the matched BC patient. A wash-out period of 5 years was applied to identify incident cases of CVD. Results The study population included 27,535 patients with BC and 269,9994 matched controls. Median age in both groups was 62 years (IQR: 20). Prior to index date, there were no significant differences in the prevalence of heart valve disease, chronic ischemic heart disease heart failure and peripheral vascular disease in BC patients compared to controls (p>0.05) (Table 1). Hypertensive heart disease, pulmonary embolism, atrial fibrillation, and other cardiac arrythmias were more prevalent in BC patients, while angina pectoris and acute myocardial infarction were more prevalent among controls. After the index date, the incidence proportion for heart valve disease, hypertensive heart disease, pulmonary embolism, atrial fibrillation, other cardiac arrythmias, and heart failure were higher in BC patients compared to controls (p<0.001) (Table 2). No significant differences were found for angina pectoris, acute myocardial infarction, chronic ischemic heart disease, and peripheral vascular disease. Conclusion Breast cancer is still associated with an increased risk of developing several CVDs in current clinical practice, compared to matched controls without breast cancer.Baseline characteristicsIncidence of CVD

Healthcare utilization in general practice and hospitals preceding a diagnosis of systemic sclerosis: a nationwide registry study.

Irreversible tissue damage is frequently present at the time of diagnosis in systemic sclerosis (SSc), which calls for earlier diagnosis. This study estimated healthcare utilization three years before the diagnosis of SSc. We conducted a population-based cohort study using data from Danish national registries. Incident patients diagnosed with SSc between January 1, 2005, and December 31, 2018, were matched by age and gender with 10 references without SSc. The date of diagnosis was the index date. We estimated quarterly rates and adjusted incidence rate ratios (IRRs) with 95% confidence intervals (CI) of healthcare utilization in the three years preceding the diagnosis for patients with SSc and their references. A total of 1,650 SSc patients (1,255 women and 395 men) and 16 500 non-SSc references were included. The mean age was 58 years (interquartile range 48-68). Three years before diagnosis, patients with SSc had more contacts with general practice (IRRwomen= 1.43 [95% CI: 1.33; 1.53], IRRmen= 1.47 [95% CI: 1.26; 1.71]) and hospitals (IRRwomen= 1.86 [95% CI: 1.62; 2.14], IRRmen= 2.70 [95% CI: 2.04; 3.58]) compared with their references. In the last three months before diagnosis, patients with SSc had significantly more contacts with general practice (IRRwomen= 2.30 [95% CI: 2.16; 2.44], IRRmen= 2.98 [95% CI: 2.64; 3.35]) and hospitals (IRRwomen= 5.62 [95% CI: 5.08; 6.20], IRRmen= 9.53 [95% CI: 7.81; 11.63]). The higher use of healthcare services in general practice and hospitals in the three years before diagnosis suggests an opportunity to facilitate earlier diagnosis and treatment of SSc.

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.

LDL-C target attainment and statin use in patients with ASCVD, familial hypercholesterolaemia, and those otherwise at moderate/high-risk of ASCVD in australian general practice (SCOPE-GP)

Abstract Background The proportion of Australian general practice patients not attaining low-density lipoprotein cholesterol (LDL-C) goals is not well described. The SCOPE-GP study evaluated duration of LDL-C exceeding treatment goals, statin use and discontinuation rates in patients with atherosclerotic cardiovascular disease (ASCVD), without ASCVD events but at moderate/high-risk, and familial hypercholesterolemia (FH). Methods This population-based retrospective cohort study used de-identified medical records of adult patients captured in the IQVIA GP-EMR database. Patients were indexed at the earliest date of ASCVD, FH, or hyperlipidemia diagnosis from January 1, 2010 to June 30, 2022, with a variable follow-up period from index to June 30, 2022. Ascertainment of study cohort was based on the 2021 ESC/EAS guidelines and Framingham Risk Equation. LDL-C test result levels were extracted per patient, summarised and analysed. Patients were stratified based on their test results at latest results/closest to censor date. Average time above target levels is the proportion of number of days above LDL-C target levels over total number of follow-up days for each patient. A Poisson distribution was fitted to estimate 95% confidence interval. Lipid lowering therapies (LLT) were stratified by (ASCVD, FH and moderate/high risk of CVD) at last visit/censor date. Combination of LLT were defined as prescriptions for fixed dose combinations or ≥2 separate scripts of LLT from different classes within 180 days from last visit/censor date (look back period). Discontinuation is defined as no statins were prescribed again after the last script for 270 days or more, limited to the first occurrence. Results The average time with LDL-C levels above target was 1077.5 days in ASCVD patients (n=2,688), 938.6 days in moderate-risk ASCVD (n=37,003), 980.9 days in high-risk ASCVD (n=85,199), and 900.8 days in FH (n=279). The proportion of days above target level for all four cohorts is described in Figure 1. Among 107,552 patients with recorded LDL-C levels ≥1.8mmol/L at their last visit/censor date, 30.9% were on statin monotherapy and 1.0% were on statin+ezetimibe. Statin use was highest in ASCVD patients (65.4%), followed by FH (49.5%), high risk (40.0%) and moderate risk subjects (29.5%) (Table 1). Statin discontinuation rates were 60.3%, 76.3, 66.1%, and 65.8% in these groups, respectively. The predominant reason for statin discontinuation was non-specific adverse drug reactions (12.2% ASCVD, 11.7% moderate-risk, 13.2% high-risk and 17.9% FH). The proportion of subjects contraindicated to statins was highest in moderate risk subjects (0.05%). Conclusions Prolonged periods of elevated LDL-C and high statin discontinuation rates were prevalent among at-risk individuals in Australian primary care. This underscores a significant ASCVD burden that could be prevented with more active lipid management.

Risk of cardiovascular disease in Hodgkin lymphoma patients

Abstract Background Cardiovascular diseases are recognized as some of the most common and problematic late complications to the treatment of Hodgkin lymphoma (HL). However, the anticipated risk is predominantly based on studies of patients treated several decades ago with treatment regimens considered outdated by todays standard. Purpose To describe the risk of cardiovascular disease in HL patients undergoing contemporary treatment regimens and comparing this risk to matched comparators. Methods A register-based cohort study including all Danish HL patients ≥18 years at diagnosis, treated with anthracycline-containing chemotherapy between 2000 and 2022. Index date was defined as date of HL diagnosis. Matching with comparators from the background population was performed in a 1:5 ratio on age, sex, and comorbidities. Patients and comparators with malignancy and/or heart disease prior to the index date were excluded. The primary outcome was a composite endpoint of cardiovascular diseases: heart failure, ischemic heart disease, diseases of the aortic-, mitral-, and tricuspid valve, constrictive pericarditis, cardiomyopathies, atrial and ventricular arrythmias, or any invasive procedures related to these diagnoses. Follow-up began at index date and ended upon event, relapse, death, emigration, or end of follow-up (December 31, 2022), whichever occurred first. The cause-specific cumulative incidence of the primary outcome was computed with all-cause death and lymphoma relapse as competing events using the Aalen-Johansen estimator. Exploratory multivariable Cox regression analyses were performed to identify risk factors for cardiovascular disease among patients with HL. Risk factors were adjusted for sex, age, and comorbidities. Results A total of 1,917 HL patients and 9,585 matched comparators were included. Median age at diagnosis was 39 years (interquartile range [IQR]: 27-56), 57% were male, and median follow-up time was 10.2 years (IQR: 5.3-15.5). The majority of patients were treated with ABVD (83%) and the estimated median cumulative anthracycline dose was 250 mg/m2 (IQR: 200-300). During the study period, 50% of patients received radiotherapy. The cause-specific cumulative incidence of the primary outcome was higher among HL patients compared with comparators across follow-up: 3.7% (95% confidence interval: 2.8-4.6) vs. 2.0% (95% CI: 1.7-2.3) at 5 years, 7.2% (95% CI: 5.7-8.7) vs. 4.6% (95% CI: 4.1-5.1) at 10 years, and 14.2% (95% CI 11.6-16.9) vs 6.7% (95% CI: 6.0-7.5) at 15 years (Figure 1). Risk factors associated with development of heart disease in HL patients were history of hypertension (HR=1.81, 95% CI 1.15-2.84) and male sex (HR=2.01, 95% CI 1.39-2.91) (Figure 2). Conclusions The long-term risk of cardiovascular disease is still high in patients with HL after contemporary treatment suggesting that the use of modern radiotherapy has not eliminated the excess risk of cardiovascular disease.

Temporal trends in treatment patterns, morbidity, and mortality in patients with new-onset heart failure compared to heart failure survivors: a nationwide 23-year perspective

Abstract Background New therapy options have improved the prognosis of heart failure (HF) over recent decades. However, temporal trends in the prognosis and treatment disparities between patients with new-onset HF and HF survivors remain unexplored. Purpose To investigate temporal trends in HF treatment patterns, worsening HF and all-cause mortality, in new-onset HF patients compared to HF survivors. Methods We defined two separate cohorts of patients with HF, using the Danish nationwide registers. One cohort comprised all patients with new-onset HF each year from 1996 to 2018, included at the date of HF diagnosis (new-onset HF patients). The second cohort comprised patients with HF who have survived at least three years since being diagnosed with HF, included on January 1st of each year from 1996 to 2018 (HF survivors). Patients were allowed to contribute in both cohorts. The proportion of patients in guideline recommended therapy and the absolute five-year risk of worsening HF and all-cause mortality were assessed in the two cohorts separately, accounting for competing risks where relevant. Results From 1996 to 2018, the proportion of HF survivors tripled, while the number of yearly new-onset HF patients remained constant (figure 1). The proportion of new-onset HF patients who redeemed a prescription of BB increased from 17.1% in 1996 to 78.2% in 2018, while it increased from 15.9% to 69.4% in HF survivors during the same period. The proportion of patients in ACEi/ARB therapy increased from 49.1% to 81.5% in the new-onset HF patients, while it increased from 37.8% to 69.0% in HF survivors. The proportion of patients in MRA therapy increased from 14.4 to 33.0% in those with new-onset HF, and from 19.1% to 24.8% in HF survivors. The absolute risk (AR)[±95CI] for all-cause mortality decreased from 68.4% [67.9-68.9] in the first year group (1996-2000) to 45.7% [45.0-46.3] in the latest year group (2013-2018) for new-onset HF patients, while it decreased from 58.4% [58.2-58.9] to 39.7% [39.4-40.0] for the HF survivors. Additionally, the AR for worsening HF went from 27.4% [26.9-27.8] in the first year group to 27.8% [27.3-28.2] in the latest year group for the new-onset HF patients, whereas it for the HF survivors decreased from 19.6% [19.3-20.0] to 16.7% [16.4-19.9]. Conclusions Over a 23-year period, the annual number of patients with incident HF has remained constant while the number of HF survivors has increased by 304%. Although HF survivors show a lower prescription redemption prevalence for essential HF medications compared to incident HF patients, they exhibit significantly lower risk of all-cause mortality and worsening HF.Figure 1:OverviewFigure 2:Prescription redememption rates

Delays in diagnosis and treatment initiation of ATTR cardiac amyloidosis: a real-world data analysis

Abstract Introduction Cardiac amyloidosis (CA) is a serious condition characterized by the accumulation of abnormal protein deposits in the heart muscle, leading to functional impairments and, ultimately, heart failure. Transthyretin amyloid cardiomyopathy (ATTR-CM) is the most common form encountered in CA diagnosis with previously underestimated prevalence. ATTR-CM poses a diagnostic challenge, with a substantial number of cases diagnosed late and at advanced stages. The availability of specific pharmacological treatment using the transthyretin-stabilizer tafamidis further emphasizes the need for timely diagnosis. Here, we aim to assess delays in diagnosis and initiation of therapy in a real-world collective of patients with ATTR-CM. Methods All individuals diagnosed from 01/2018 to 05/2023 with ATTR-CM at our university hospital, Germany, were systematically assessed for eligibility in this study. Specifically, we enrolled patients who were undergoing transthyretin stabilizer therapy. The investigation aimed to determine the duration, in days, from the initial suspicion of heart disease to the definitive diagnosis of ATTR-CM. It was also investigated whether the diagnosis of ATTR-CM was made more quickly over time as awareness increased. Additionally, the study assessed the time elapsed until patients received pharmacological therapy following the confirmed diagnosis. The study was approved by the local ethics committee (23-11500-BO). Results After screening of 194 consecutive patients, 154 were included in the analysis, while 40 patients were excluded due to insufficient records. The results of this study reveal that a median of 300 (113-962) days elapsed from the initial suspicion of amyloidosis to the final confirmation. Initial indications of CA often presented as nonspecific symptoms such as unclear dyspnea (16.2% n=25), abnormal echocardiography (75.3% n=116), or, in rare cases, incidental findings (8.4% n=13). Following the diagnosis, an additional median of 84 (46-163.5) days passed before the first prescription of a transthyretin stabilizer. To assess an improvement of ATTR-CM diagnosis over time, we stratified the data into tertiles by date of first diagnosis. The results showed a gradually decrease in medium time to diagnosis of 466 (181-1035) days in the earliest tertile (2018-2019) to 389 (141-1508) days in the most recent tertile (2022-2023) (p<0.001). Conclusion This study shows a major healthcare deficit and underscores the medical need for improved screening procedures and diagnostic modalities to expedite the timely diagnosis of CA, as early identification of the condition is crucial for enhancing the quality of life for patients and preventing life-threatening complications.

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.