Population-based Cohort Of Patients Research Articles

Association between statin use and the prognosis of hepatocellular carcinoma after resection: a nationwide cohort study

The majority of patients with hepatocellular carcinoma (HCC) following hepatic resection experience tumor recurrence. Statin use is associated with a reduced risk of HCC development; however, the association between statin use and the prognosis of HCC after resection remains unclear. We aimed to investigate the effect of statin use on the prognosis after hepatic resection among patients with HCC. A nationwide cohort study was performed with data from the National Health Insurance Service Database in Korea. Among 65,101 HCC patients who underwent hepatic resection between January 2002 and December 2017, we included 21,470 patients. For validation, a hospital-based cohort of 3366 patients with very early or early-stage HCC who received curative-intent hepatic resection between January 2010 and December 2018 was analyzed. Recurrence-free survival (RFS) and overall survival (OS) was compared between statin users and non-users. Among the nationwide cohort of 21,470 patients, 2399 (11.2%) used statins and 19,071 (88.8%) did not. Among the hospital cohort of 3366 patients, 363 (10.8%) used statins and 3003 (89.2%) did not. In the propensity score-matched nationwide cohort, statin users had better RFS (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.56-0.64; P<0.001) and OS (HR, 0.49; 95% CI, 0.45-0.53; P<0.001), with a duration-response relationship. In the propensity score-matched validation hospital cohort, statin treatment was significantly associated with better RFS (HR, 0.73; 95% CI, 0.59-0.90; P=0.003) and OS (HR, 0.48; 95% CI, 0.32-0.72; P<0.001). The beneficial effects of statins were more prominent in non-cirrhotics, tumors sized ≥3cm, tumors with microscopic vascular invasion, or early HCC recurrence (<2 years after resection). Statin use was associated with a better prognosis in a population-based cohort of patients with HCC after hepatic resection, which was further validated in a large hospital-based cohort. Asan Institute for Life Sciences and Corporate Relations; Korean Association for the Study of the Liver.

Association between hospital onset of infection and outcomes in sepsis patients – A propensity score matched cohort study based on health claims data in Germany

BackgroundHospital-acquired infections are a common source of sepsis. Hospital onset of sepsis was found to be associated with higher acute mortality and hospital costs, yet its impact on long-term patient-relevant outcomes and costs is unknown. ObjectiveWe aimed to assess the association between sepsis origin and acute and long-term outcomes based on a nationwide population-based cohort of sepsis patients in Germany. MethodsThis retrospective cohort study used nationwide health claims data from 23 million health insurance beneficiaries. Sepsis patients with hospital-acquired infections (HAI) were identified by ICD-10-codes in a cohort of adult patients with hospital-treated sepsis between 2013 and 2014. Cases without these ICD-10-codes were considered as sepsis cases with community-acquired infection (CAI) and were matched with HAI sepsis patients by propensity score matching. Outcomes included in-hospital/12-month mortality and costs, as well as readmissions and nursing care dependency until 12 months postsepsis. ResultsWe matched 33,110 HAI sepsis patients with 28,614 CAI sepsis patients and 22,234 HAI sepsis hospital survivors with 19,364 CAI sepsis hospital survivors. HAI sepsis patients had a higher hospital mortality than CAI sepsis patients (32.8% vs. 25.4%, RR 1.3, p < .001). Similarly, 12-months postacute mortality was higher (37.2% vs. 30.1%, RR=1.2, p < .001). Hospital and 12-month health care costs were 178% and 22% higher in HAI patients than in CAI patients, respectively. Twelve months postsepsis, HAI sepsis survivors were more often newly dependent on nursing care (33.4% vs. 24.0%, RR=1.4, p < .001) and experienced 5% more hospital readmissions (mean number of readmissions: 2.1 vs. 2.0, p < .001). ConclusionsHAI sepsis patients face an increased risk of adverse outcomes both during the acute sepsis episode and in the long-term. Measures to prevent HAI and its progression into sepsis may be an opportunity to mitigate the burden of long-term impairments and costs of sepsis, e.g., by early detection of HAI progressing into sepsis, particularly in normal wards; adequate sepsis management and adherence to sepsis bundles in hospital-acquired sepsis; and an improved infection prevention and control.

Pembrolizumab vs chemotherapy in the first-line setting of PD-L1≥50% metastatic non-small cell lung cancer: A real-world cost-effectiveness analysis.

21 Background: Despite the voiced concerns around the initial economic decision models for first-line pembrolizumab in PD-L1≥50% metastatic non-small cell lung cancer (mNSCLC), there has been a paucity of evidence on the anticipated cost-effectiveness of pembrolizumab in the real world. To resolve the uncertainties associated with the initial assessment, we evaluated the real-world cost-effectiveness of first line pembrolizumab versus platinum-based chemotherapy for mNSCLC patients with PD-L1≥50%. Methods: We retrospectively identified a population-based cohort of mNSCLC patients who received first-line pembrolizumab or platinum-based chemotherapy between April 1, 2013, and March 31, 2021, in Ontario, Canada. Employing a public payer’s perspective, all costs (in Canadian dollars) and effects were estimated over a 4-year horizon, adjusted for censoring and discounted at 1.5% yearly. The primary outcomes were incremental cost-effectiveness ratios (ICERs) for life-years gained (LYG) and quality-adjusted life year (QALY). To examine the sensitivity of the ICER to drug acquisition costs and discounting, we conducted a price reduction analysis and a scenario analysis of different discount rates. Results: Propensity-score matching resulted in a total of 1,142 pairs of matched mNSCLC patients. Pembrolizumab extended survival with an incremental effect of 0.37 LYG and 0.35 QALY, but at an incremental cost of $56,681; the resulting ICERs were $154,941/LYG and $163,039/QALY. Though the ICERs were not sensitive to discounting rate, 31% and 55% reductions to the price of pembrolizumab brought the ICER below $100,000/QALY and $50,000/QALY, respectively. Conclusions: In the real world, first-line pembrolizumab is not considered to be cost-effective for mNSCLC patients with PD-L1≥50%. Improvements in cost-effectiveness, however, may be achievable through price renegotiations for pembrolizumab.

Overuse of EEG and ECG in children with breath-holding spells and its implication for the management of the spells.

Breath-holding spells (BHS) are common in children, but evidence-based clinical guidelines are lacking. We investigated a large population-based cohort of BHS patients, to propose a refined description of typical BHS and guidelines for its management. In a cross-sectional retrospective study, patients diagnosed with BHS in Southern Sweden 2004-2018 were recruited. Disease characteristics and diagnostic data were collected from patient medical records. In total, 519 patients, mean age at diagnosis 19.8 ± 13.8 months with equal gender distribution, were included. In 48.3%, BHS had already been diagnosed after one spell. During spells, 78.0% of patients were unresponsive. For 71.5%, atonic, tonic, tonic-clonic or myoclonic seizures were reported, and 78.0% of patients had a spell lasting less than 1 min. Electroencephalography was conducted in 30.4% and Electrocardiography in 45.1%. Six children (3.8%) had a pathological electroencephalogram, four of which had concomitant epilepsy and only 0.9% of children had electrocardiogram findings suggesting pathology, none showing long QT syndrome. Children with BHS were frequently subjected to unnecessary diagnostic interventions. We characterise a typical presentation of BHS and propose a management-algorithm, which is expected to reduce unnecessary usage of electroencephalography and electrocardiography.

Mental health outcomes in a population-based cohort of patients with prostate cancer.

Few studies have evaluated mental health disorders comprehensively among patients with prostate cancer on long-term follow-up. The primary aim of our study was to assess the incidence of mental health disorders among patients with prostate cancer compared with a general population cohort. A secondary aim was to investigate potential risk factors for mental health disorders among patients with prostate cancer. Cohorts of 18 134 patients with prostate adenocarcinomas diagnosed between 2004 and 2017 and 73470 men without cancer matched on age, birth state, and follow-up time were identified. Mental health diagnoses were identified from electronic health records and statewide health-care facilities data. Cox proportional hazard models were used to estimate hazard ratios. All statistical tests were 2-sided. The hazard ratios for mood disorders, including depression, among prostate cancer survivors increased for all follow-up periods compared with the general population. The hazard ratios for any mental illness increased with Hispanic, Black, or multiple races; people who were underweight or obese; those with advanced prostate cancer; and those undergoing their first course cancer treatment. We also observed statistically significantly increased hazard ratios for mental health disorders among patients with lower socioeconomic status (P < .0001) and increasing duration of androgen-deprivation therapy (P = .0348). Prostate cancer survivors had a 61% increased hazard ratio for death with a depression diagnosis. Prostate cancer diagnosis was associated with a higher risk of mental health disorders compared with the general population, which was observed as long as 10-16 years after cancer diagnosis. Providing long-term mental health support may be beneficial to increasing life expectancy for patients with prostate cancer.

The Impact of Biologic Therapies on Rate of Colectomy in Paediatric-onset Ulcerative Colitis - A Population-Based Cohort Study

AimBiologic therapies have been associated with reduced rate of colectomy in ulcerative colitis (UC) in adults, but data are limited in paediatric-onset UC. Our aim was to define the rate of colectomy in paediatric-onset UC, including post-transition into adult care, and to evaluate the impact of biologic therapies on rate of colectomy. MethodAll prevalent patients diagnosed with paediatric-onset UC in South-East Scotland were identified from a prospectively accrued database at our regional tertiary centre. Patients exposed to biologics or surgery were identified and further data collected from health records. Kaplan–Meier analysis was used to calculate cumulative risk of colectomy over time. Results145 prevalent patients were identified between 2000 and 2021. Median follow-up was 7.9 years (IQR 4.1–13.1). 23 patients (16 %) underwent a colectomy. 50/145 (34 %) patients received biologic therapy, and 13/23 (57 %) patients who underwent colectomy received biologics. The cumulative risk of colectomy across the whole cohort at 1, 5, and 10 years was 3 %, 13 % and 16 %, respectively. Patients exposed to biologics had a higher colectomy rate at 5 and 10 years (22 % and 34 %). Patients in the pre-biologic era (2000–2008) had non-significantly reduced time from diagnosis to colectomy (2.4 vs 3.7 years, p = 0.204). ConclusionWe have defined the 1-, 5-, and 10-year colectomy rate in a population-based cohort of Paediatric-onset UC patients. Patients who received biologic therapy had a significantly increased risk of colectomy. Increased severity of disease in these patients may account for the greater colectomy risk. Level of EvidenceLevel 1.

Mortality in Patients With Primary Aldosteronism: A Swedish Nationwide Study.

Primary aldosteronism (PA) is associated with increased mortality. The extent to which this phenomenon is affected by gender, age, comorbidities at diagnosis, and different treatment modalities is largely unknown. The objective was to determine all-cause and cause-specific mortality in a population-based cohort of patients with PA and the impact of age at diagnosis, sex, comorbidities, and treatment modalities. We used national registers to identify patients diagnosed with PA between 1997 and 2019 (n=2419) and controls (n=24 187) from the general population, matched for sex, age, and county of residence. We obtained mortality data from the Cause-of-Death Register. We used Cox regression models, adjusted for socioeconomic factors and diabetes, to estimate adjusted hazard ratios (HRs [95% CI]). Overall, 346 (14.3%) patients with PA and 2736 (11.3%) controls died during a median follow-up time of 8.1 years. PA was associated with increased risk from all-cause mortality (HR, 1.23 [95% CI, 1.10-1.38]), death from cardiovascular disease (HR, 1.57 [95% CI, 1.30-1.89]), and stroke (HR, 1.85 [95% CI, 1.16-2.93]). Patients with cardiovascular disease at diagnosis (HR, 1.53 [1.26-1.85]), age >56 years (HR, 1.28 [95% CI, 1.13-1.45]), patients treated with a low dose of a mineralocorticoid receptor antagonist (HR, 1.30 [95% CI, 1.02-1.66]), and untreated patients (HR, 2.51 [95% CI, 1.72-3.67]) had excess mortality. Mortality, mainly due to cardiovascular disease, is increased in patients with PA compared with controls from the general population, particularly in patients aged >56 years, patients with preexisting cardiovascular comorbidities, and patients receiving low dose of a mineralocorticoid receptor antagonist.

Comparison of SP142 and 22C3 PD-L1 assays in a population-based cohort of triple-negative breast cancer patients in the context of their clinically established scoring algorithms

BackgroundImmunohistochemical (IHC) PD-L1 expression is commonly employed as predictive biomarker for checkpoint inhibitors in triple-negative breast cancer (TNBC). However, IHC evaluation methods are non-uniform and further studies are needed to optimize clinical utility.MethodsWe compared the concordance, prognostic value and gene expression between PD-L1 IHC expression by SP142 immune cell (IC) score and 22C3 combined positive score (CPS; companion IHC diagnostic assays for atezolizumab and pembrolizumab, respectively) in a population-based cohort of 232 early-stage TNBC patients.ResultsThe expression rates of PD-L1 for SP142 IC ≥ 1%, 22C3 CPS ≥ 10, 22C3 CPS ≥ 1 and 22C3 IC ≥ 1% were 50.9%, 27.2%, 53.9% and 41.8%, respectively. The analytical concordance (kappa values) between SP142 IC+ and these three different 22C3 scorings were 73.7% (0.48, weak agreement), 81.5% (0.63) and 86.6% (0.73), respectively. The SP142 assay was better at identifying 22C3 positive tumors than the 22C3 assay was at detecting SP142 positive tumors. PD-L1 (CD274) gene expression (mRNA) showed a strong positive association with all two-categorical IHC scorings of the PD-L1 expression, irrespective of antibody and cut-off (Spearman Rho ranged from 0.59 to 0.62; all p-values < 0.001). PD-L1 IHC positivity and abundance of tumor infiltrating lymphocytes were of positive prognostic value in univariable regression analyses in patients treated with (neo)adjuvant chemotherapy, where it was strongest for 22C3 CPS ≥ 10 and distant relapse-free interval (HR = 0.18, p = 0.019). However, PD-L1 status was not independently prognostic when adjusting for abundance of tumor infiltrating lymphocytes in multivariable analyses.ConclusionOur findings support that the SP142 and 22C3 IHC assays, with their respective clinically applied scoring algorithms, are not analytically equivalent where they identify partially non-overlapping subpopulations of TNBC patients and cannot be substituted with one another regarding PD-L1 detection.Trial registration The Swedish Cancerome Analysis Network - Breast (SCAN-B) study, retrospectively registered 2nd Dec 2014 at ClinicalTrials.gov; ID NCT02306096.

FRI182 Cardiometabolic Risk And Outcomes In Patient With Adrenal Adenomas

Abstract Disclosure: H. Lam: None. H. Han: None. S. Athimulam: None. Background: Approximately 5% of adults undergoing cross-sectional imaging are reported to have an adrenal adenoma. Although most adenomas are considered non-functioning (NFAT), up to 48% can present with mild autonomous cortisol secretion (MACS). Published studies have reported an increased prevalence of cardiometabolic risk factors, cardiac and cerebrovascular events in MACS patients. Objective: To determine the prevalence of cardiometabolic disease and outcomes in a population-based cohort of patients with adrenal adenomas. Design: Retrospective cross-sectional study of patients with adrenal adenomas over a 10-year period (Jan 2012 – Dec 2021). Setting: Academic primary and tertiary care setting. Main outcomes measured: Prevalence of cardiometabolic disease, cardiovascular events requiring procedure (percutaneous coronary intervention, PCI or coronary artery bypass graft, CABG) and cerebrovascular events. MACS was diagnosed based on cortisol level ≥ 1.8cmg/dL after overnight 1mg dexamethasone suppression testing (DST) and NFAT if cortisol &amp;lt; 1.8mcg/dL. Patients who did not undergo 1mg DST were categorized as unknown cortisol status (UCS). Results: Preliminary results include 198 patients with adrenal adenomas [(135 women (67%) with a median age of 67y, 106 Black (54%), 83 White (42%) and 9 other races (4%)]. 74 (37%) were diagnosed with NFAT, 42 (21%) with MACS, and 82 (41%) with UCS. Hypertension (n=163,83%; MACS vs NFAT vs UCS: 23% vs 34% vs 43%) is the most prevalent cardiometabolic risk factor, followed by hyperlipidemia (n=146, 75%; MACS vs NFAT vs UCS: 21% vs 38% vs 41%), prediabetes (n=94, 50%; MACS vs NFAT vs UCS: 18% vs 43% vs 39%) and type 2 diabetes mellitus (n=82,43%; MACS vs NFAT vs UCS: 22% vs 35% vs 43%), respectively. 14% of patients with adrenal adenomas underwent procedures (PCI or CABG) for cardiovascular events (MACS vs NFAT vs UCS: 33% vs 26% vs 41%) and 11% were diagnosed with cerebrovascular events (MACS vs NFAT vs UCS: 29% vs 19% vs 52%). Conclusions: Patients with adrenal adenomas and mild autonomous cortisol secretion (MACS) are at increased risk of cardiovascular events requiring intervention and cerebrovascular events, compared to non-functioning adrenal tumors. 41% (n=82, 61% Blacks, 30% White, 2% Others) of patient population was classified as unknown cortisol status indicating further need to educate health care professionals on evaluation of adrenal adenomas to improve health care outcomes and disparities in management. Presentation: Friday, June 16, 2023

THU338 Risks Of Stroke, Its Subtypes And Atrial Fibrillation Associated With Glucagon-like Peptide 1 Receptor Agonists Versus Sodium-glucose Cotransporter 2 Inhibitors: A Real-world Population-based Study In Hong Kong

Abstract Disclosure: D. Lui: None. E. Tang: None. T. Wu: None. I. Au: None. C. Lee: None. Y. Woo: None. K.C. Tan: None. C. Wong: None. Objectives: There are limited data on head-to-head comparative risk of stroke between sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA). Such a comparison may provide further insights in the selection of appropriate anti-diabetic agents. We compared risk of stroke with its subtypes and incident atrial fibrillation (AF) between them in a population-based cohort. Methods: A population-based cohort of adult patients (aged 18 years or above) with type 2 diabetes between 2008 and 2020 were identified from the electronic health records of Hong Kong Hospital Authority. Patients who received SGLT2i or GLP-1RA were matched pairwise by propensity score. The index date of each patient was set at the date of SGLT2i or GLP-1RA initiation. Patients with end-stage kidney disease or co-initiation of SGLT2i and GLP-1RA at the index date were excluded. The primary outcome was all events of stroke, consisting of hemorrhagic and ischemic stroke. Secondary outcomes included hemorrhagic stroke, ischemic stroke, incident AF, and cardioembolic stroke. Each patient was observed from the index date until the occurrence of events, death, treatment cross-over, or end-of-study (31 December 2020), whichever was earlier. Risks of stroke and AF were evaluated by hazard ratios (HRs) from the Cox proportional hazard regression models. Results: A total of 5,840 patients (2,920 SGLT2i users; 2,920 GLP-1RA users) were included (mean age 55.5 years, 56.1% men, mean HbA1c 8.9% and duration of diabetes 13.7 years). Upon median follow-up of 17 months (IQR: 8-34), there were 111 events of stroke. SGLT2i users had comparable risk of all stroke as GLP-1RA users (HR=1.46, 95%CI 0.99-2.17, p=0.058). SGLT2i users had higher risk of ischemic stroke (HR=1.53, 95%CI 1.01-2.33, p=0.044) but similar risk of hemorrhagic stroke (HR=1.29, 95%CI: 0.53-3.14, p=0.582) compared to GLP-1RA users. Although SGLT2i was associated with lower risk of incident AF (HR=0.43, 95%CI 0.23-0.79, p=0.006), risk of cardioembolic stroke was similar (HR=1.40, 95%CI: 0.62-3.17, p=0.414). Subgroup analyses showed no significant interaction between subgroups by age, sex, glycemic control and history of AF. However, patients with history of stroke appeared to benefit more from GLP-1RA use (p for interaction=0.043) than those without history of stroke. Patients with shorter duration of diabetes (&amp;lt;10 years) also appeared to benefit more from GLP-1RA use than those with longer duration of diabetes (p for interaction=0.017). Conclusions: Our real-world study demonstrated that GLP-1RA use was associated with lower risk of ischemic stroke, despite the association between SGLT2i use and lower risk of incident AF. There was no significant difference in hemorrhagic stroke risk. GLP-1RA may be the preferred agent for patients with type 2 diabetes at risk of ischemic stroke. Presentation: Thursday, June 15, 2023

1137P Treatment strategies and survival outcomes in a nationwide, population-based cohort of patients with melanoma brain metastases: The role of planned shift in systemic therapy and postoperative stereotactic radiotherapy

1137P Treatment strategies and survival outcomes in a nationwide, population-based cohort of patients with melanoma brain metastases: The role of planned shift in systemic therapy and postoperative stereotactic radiotherapy

Toxoplasma gondii and multiple sclerosis: a population-based case-control seroprevalence study, Central Anatolia, Turkey.

Toxoplasma gondii, an obligate intracellular parasite, is prevalent in various mammalian species, as well as certain avian, reptilian, and cold-blooded organisms. While immunocompetent individuals generally remain asymptomatic, immunocompromised individuals may experience severe and life-threatening conditions. Multiple sclerosis (MS), a chronic autoimmune disease affecting the central nervous system (CNS), is characterized by inflammation, demyelination, and axonal damage. Despite extensive research, the etiology and pathogenesis of MS remain incompletely understood. Given the strong affinity of T. gondii for the CNS, researchers have explored the potential association between T. gondii and autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, type 1 diabetes, and MS. This study aimed to investigate the possible relationship between MS and T. gondii. A population-based incident cohort of MS patients in Sivas, Turkey, was used to randomly select MS patients. Age- and sex-matched controls were also randomly selected from the general population. A total of 182 MS patients and 182 controls were included in the study. Clinical and socio-demographic variables were recorded using a structured questionnaire. Blood samples were collected from MS patients, and Toxoplasma IgG and IgM antibodies were measured using the enzyme-linked immunosorbent assay technique. Anti-Toxoplasma IgG antibodies were detected in 78 cases (42.9%) and 73 controls (40.1%) (p>0.05). Age, female sex, and consumption of raw meat were identified as risk factors for toxoplasmosis in both MS patients and controls. In contrast to previous studies, this study did not find a significant difference in T. gondii seropositivity between the control group and MS patients. Further investigations are recommended to elucidate the precise relationship between MS patients and T. gondii.

Machine Learning-Based Early Warning Systems for Acute Care Utilization During Systemic Therapy for Cancer.

Emergency department visits and hospitalizations frequently occur during systemic therapy for cancer. We developed and evaluated a longitudinal warning system for acute care use. Using a retrospective population-based cohort of patients who started intravenous systemic therapy for nonhematologic cancers between July 1, 2014, and June 30, 2020, we randomly separated patients into cohorts for model training, hyperparameter tuning and model selection, and system testing. Predictive features included static features, such as demographics, cancer type, and treatment regimens, and dynamic features, such as patient-reported symptoms and laboratory values. The longitudinal warning system predicted the probability of acute care utilization within 30 days after each treatment session. Machine learning systems were developed in the training and tuning cohorts and evaluated in the testing cohort. Sensitivity analyses considered feature importance, other acute care endpoints, and performance within subgroups. The cohort included 105,129 patients who received 1,216,385 treatment sessions. Acute care followed 182,444 (15.0%) treatments within 30 days. The ensemble model achieved an area under the receiver operating characteristic curve of 0.742 (95% CI, 0.739-0.745) and was well calibrated in the test cohort. Important predictive features included prior acute care use, treatment regimen, and laboratory tests. If the system was set to alarm approximately once every 15 treatments, 25.5% of acute care events would be preceded by an alarm, and 47.4% of patients would experience acute care after an alarm. The system underestimated risk for some treatment regimens and potentially underserved populations such as females and non-English speakers. Machine learning warning systems can detect patients at risk for acute care utilization, which can aid in preventive intervention and facilitate tailored treatment. Future research should address potential biases and prospectively evaluate impact after system deployment.

Chronic myeloid leukaemia: A qualitative interview study exploring disease impact from patient and practitioner perspectives

PurposeImprovements in chronic myeloid leukaemia treatment mean it is now relevant to examine the experiences of living with this cancer over a lifetime. This qualitative study aimed to investigate the impact of chronic myeloid leukaemia, from patient and healthcare practitioner perspectives. MethodsThe research was set within the UK's Haematological Malignancy Research Network; a population-based cohort of patients newly diagnosed with blood cancer, treated at one of fourteen hospitals. Purposive sampling led to interviews with seventeen patients and thirteen health care practitioners. Data were analysed using thematic analysis. ResultsTwo analytical themes, “Significant impact of disease and treatment” and “Mediators of the impact of disease and treatment”, and six sub-themes, were derived from patient interviews and supported with data from practitioners. Chronic myeloid leukaemia was described by patients as having significant widespread impact, which could be mediated by their knowledge, social support, and the quality of healthcare systems. Practitioners reflected patient accounts, but could underestimate the impact of this cancer. They generally viewed chronic myeloid leukaemia as less complex, severe and impactful than acute blood cancers; a message that reassured patients at diagnosis, but could later unintentionally contribute to difficulties discussing side effects and struggles to cope. ConclusionChronic myeloid leukaemia may significantly impact individuals, particularly as it is experienced over the lifetime. Greater understanding and discussion of the breadth and extent to which patients are affected, including potential mediators, could enhance clinical care.

Novel methods to define invasive procedures at the end of life were developed to improve quality of end of life care research: a population-based cohort study in colorectal cancer

BackgroundUnderstanding the use of invasive procedures (IPs) at the end of life (EoL) is important to avoid undertreatment and overtreatment, but epidemiologic analysis is hampered by limited methods to define treatment intent and EoL phase. This study applied novel methods to report IPs at the EoL using a colorectal cancer case study. MethodsAn English population-based cohort of adult patients diagnosed between 2013 and 2015 was used with follow-up to 2018. Procedure intent (curative, noncurative, diagnostic) by cancer site and stage at diagnosis was classified by two surgeons independently. Joinpoint regression modeled weekly rates of IPs for 36 subcohorts of patients with incremental survival of 0–36 months. EoL phase was defined by a significant IP rate change before death. Zero-inflated Poisson regression explored associations between IP rates and clinical/sociodemographic variables. ResultsOf 87,731 patients included, 41,972 (48%) died. Nine thousand four hundred ninety two procedures were classified by intent (inter-rater agreement 99.8%). Patients received 502,895 IPs (1.39 and 3.36 per person year for survivors and decedents). Joinpoint regression identified significant increases in IPs 4 weeks before death in those living 3–6 months and 8 weeks before death in those living 7–36 months from diagnosis. Seven thousand nine hundred eight (18.8%) patients underwent IPs at the EoL, with stoma formation the most common major procedure. Younger age, early-stage disease, men, lower comorbidity, those receiving chemotherapy, and living longer from diagnosis were associated with IPs. ConclusionMethods to identify and classify IPs at the EoL were developed and tested within a colorectal cancer population. This approach can be now extended and validated to identify potential undertreatment and overtreatment.

Genome-wide study of genetic polymorphisms predictive for outcome from first-line oxaliplatin-based chemotherapy in colorectal cancer patients.

We conducted the first large genome-wide association study to identify novel genetic variants that predict better (or poorer) prognosis in colorectal cancer patients receiving standard first-line oxaliplatin-based chemotherapy vs chemotherapy without oxaliplatin. We used data from two phase III trials, NCCTG N0147 and NCCTG N9741 and a population-based patient cohort, DACHS. Multivariable Cox proportional hazards models were employed, including an interaction term between each SNP and type of treatment for overall survival (OS) and progression-free survival. The analysis was performed for studies individually, and the results were combined using fixed-effect meta-analyses separately for resected stage III colon cancer (3098 patients from NCCTG N0147 and 549 patients from DACHS) and mCRC (505 patients from NCCTG N9741 and 437 patients from DACHS). We further performed gene-based analysis as well as in silico bioinformatics analysis for CRC-relevant functional genomic annotation of identified loci. In stage III colon cancer patients, a locus on chr22 (rs11912167) was associated with significantly poorer OS after oxaliplatin-based chemotherapy vs chemotherapy without oxaliplatin (Pinteraction < 5 × 10-8 ). For mCRC patients, three loci on chr1 (rs1234556), chr12 (rs11052270) and chr15 (rs11858406) were found to be associated with differential OS (P < 5 × 10-7 ). The locus on chr1 located in the intronic region of RCSD1 was replicated in an independent cohort of 586 mCRC patients from ALGB/SWOG 80405 (Pinteraction = .04). The GWA gene-based analysis yielded for RCSD1 the most significant association with differential OS in mCRC (P = 6.6 × 10-6 ). With further investigation into its biological mechanisms, this finding could potentially be used to individualize first-line treatment and improve clinical outcomes.

Symptoms and symptom clusters in patients newly diagnosed with inflammatory bowel disease: results from the IBSEN III Study

BackgroundPatients with inflammatory bowel disease report multiple symptoms, but the relationships among co-occurring symptoms are poorly understood. This study aimed to examine the prevalence of symptoms and explore symptom clusters and possible associations between symptom clusters and socio-demographic and clinical variables in patients newly diagnosed with inflammatory bowel disease.MethodsThe IBSEN III study is a prospective population-based inception cohort of patients with inflammatory bowel disease. This study used patient data from the three largest hospitals in the study catchment area. The Memorial Symptom Assessment Scale was used to assess the prevalence of symptoms. Symptom clusters were identified using principal component analysis. Possible associations between socio-demographic and clinical variables and symptom cluster membership were estimated using regression analysis.ResultsOf the 573 patients (age, ≥18 years) diagnosed with inflammatory bowel disease, 350 (61.1%) completed the questionnaire (responders). Eleven symptoms were reported by >50% of the responders. The three most prevalent symptoms were bloating (84%), drowsiness (81%), and lack of energy (81%). Three symptom clusters were identified: psychological (56% of the patients), impaired energy (28%), and physical (16%) clusters. Multinomial regression analysis revealed that vitamin D deficiency was significantly associated with the impaired energy cluster (odds ratio=2.49, 95% confidence interval [1.00-6.2],p=0.05).ConclusionsWe found high symptom prevalence in patients newly diagnosed with inflammatory bowel disease. Three distinct symptom clusters were identified, and the psychological cluster includes >50% of the patients. Vitamin D deficiency is the only factor associated with cluster membership, namely the impaired energy cluster.

The Metabolic Vulnerability Index: A Novel Marker for Mortality Prediction in Heart Failure

BackgroundInflammation and protein energy malnutrition are associated with heart failure (HF) mortality. The metabolic vulnerability index (MVX) is derived from markers of inflammation and malnutrition and measured by nuclear magnetic resonance spectroscopy. MVX has not been examined in HF. ObjectivesThe authors sought to examine the prognostic value of MVX in patients with HF. MethodsThe authors prospectively assembled a population-based cohort of patients with HF from 2003 to 2012 and measured MVX scores with a nuclear magnetic resonance scan from plasma collected at enrollment. Patients were divided into 4 MVX score groups and followed until March 31, 2021. ResultsThe authors studied 1,382 patients (median age: 78 years; 48% women). The median MVX score was 64.6. Patients with higher MVX were older, more likely to be male, have atrial fibrillation, and have a higher Meta-analysis Global Group in Chronic Heart Failure score. Higher MVX was associated with mortality independent of Meta-analysis Global Group in Chronic Heart Failure score, ejection fraction, and other prognostic biomarkers. Compared to those with the lowest MVX, the HRs for MVX groups 2, 3, and 4 were 1.1 (95% CI: 0.9-1.4), 1.5 (95% CI: 1.2-1.9), and 1.5 (95% CI: 1.2-1.9), respectively (Ptrend < 0.001). Measures of model improvement document the added value of MVX in HF for classifying the risk of death beyond the Meta-analysis Global Group in Chronic Heart Failure score and other biomarkers. ConclusionsIn this HF community cohort, MVX was strongly associated with mortality independently of established clinical factors and improved mortality risk classification beyond clinically validated markers. These data underscore the potential of MVX to stratify risk in HF.

Impact of Heavy Snowfall on Emergency Transport and Prognosis of Out-of-Hospital Cardiac Arrest Patients: A Nation-Wide Cohort Study.

Out-of-hospital cardiac arrest (OHCA) is a significant global cause of mortality, and Emergency Medical Services (EMS) response interval is critical for survival and a neurologically-favorable outcome. Currently, it is unclear whether EMS response interval, neurologically-intact survival, and overall survival differ between snowy and non-snowy periods at heavy snowfall areas. A nation-wide population-based cohort of OHCA patients, registered from 2017 through 2019 in the All-Japan Utstein Registry, was divided into four groups according to areas (heavy snowfall area or other area) and seasons (winter or non-winter): heavy snowfall-winter, heavy snowfall-non-winter, other area-winter, and other area-non-winter. The first coprimary outcome was EMS response interval, and the secondary coprimary outcome was one-month survival and a neurologically-favorable outcome at one month. A total of 337,781 OHCA patients were divided into four groups: heavy snowfall-winter (N = 15,627), heavy snowfall-non-winter (N = 97,441), other area-winter (N = 32,955), and other area-non-winter (N = 191,758). Longer EMS response intervals (>13 minutes) were most likely in the heavy snowfall-winter group (OR = 1.86; 95% CI, 1.76 to 1.97), and also more likely in heavy snowfall areas in non-winter (OR = 1.44; 95% CI, 1.38 to 1.50). One-month survival in winter was worse not only in the heavy snowfall area (OR = 0.86; 95% CI, 0.78 to 0.94) but also in other areas (OR = 0.91; 95% CI, 0.87 to 0.94). One-month neurologically-favorable outcomes were also comparable between heavy snowfall-winter and other area-non-winter groups. This study showed OHCA in heavy snowfall areas in winter resulted in longer EMS response intervals. However, heavy snowfall had little effect on one-month survival or neurologically-favorable outcome at one month.

Prevalence and comorbidities of Sjogren's syndrome patients in the Community of Madrid: A population-based cross-sectional study.

To estimate the prevalence, sociodemographic characteristics and comorbidities of Sjogren's syndrome (SS) patients in the Community of Madrid. A population-based cross-sectional cohort of SS patients was derived from the information system for rare diseases in the Community of Madrid (SIERMA) and confirmed by a physician. The prevalence per 10,000 inhabitants among people aged ≥18years in June 2015 was calculated. Sociodemographic data and accompanying disorders were recorded. Univariate and bivariate analyses were performed. A total of 4,778 SS patients were confirmed in SIERMA; 92.8% were female, with a mean age of 64.3 (standard deviation=15.4) years. A total of 3,116 (65.2%) patients were classified as primary SS (pSS), and 1,662 (34.8%) as secondary SS (sSS). The prevalence of SS among people aged ≥18 years was 8.4/10,000 (95%Confidence interval [CI]=8.2-8.7). The prevalence of pSS was 5.5/10,000 (95%CI=5.3-5.7), and that of sSS was 2.8/10,000 (95%CI=2.7-2.9), with rheumatoid arthritis (20.3%) and systemic lupus erythematosus (8.5%) being the most prevalent associated autoimmune diseases. The most common comorbidities were hypertension (40.8%), lipid disorders (32.7%), osteoarthritis (27.7%) and depression (21.1%). The most prescribed medications were nonsteroidal anti-inflammatory drugs (31.9%), topical ophthalmic therapies (31.2%) and corticosteroids (28.0%). The prevalence of SS in the Community of Madrid was similar to the overall prevalence worldwide observed in previous studies. SS was more frequent in women in their sixth decade. Two out of every three SS cases were pSS, while one-third were associated predominantly with rheumatoid arthritis and systemic lupus erythematosus.