Incidence Rate Research Articles

Machine learning identifies individuals at higher risk of incident cardio-renal-metabolic diseases and cardiovascular death who have unrealised opportunities to reduce future cardiovascular risk

Abstract Background Machine learning may be able to identify individuals at risk of cardio-renal-metabolic events using routinely-collected data, and these individuals may be suitable for targeted preventative strategies.(1, 2) Purpose To train and test a machine learning algorithm to identify individuals at higher risk of incident cardio-renal-metabolic diseases and cardiovascular death, and then establish if there are opportunities to reduce their future cardiovascular risk. Methods We trained a random classifier (OPTIMISE) in UK primary care EHR data from 2 081 139 individuals aged ≥30 years (Jan 2, 1998, Nov 30, 2018), randomly divided into training (80%) and testing (20%) datasets. We calculated the cumulative incidence rate for ten cardio-renal-metabolic diseases and death. Fine and Gray’s models with competing risk of death were fit for each outcome between higher and lower predicted risk. In a multi-centre pilot interventional single arm study consenting individuals aged ≥30 years at higher predicted risk received cardio-renal-metabolic phenotyping and assessment for guideline target attainment. Results In the testing dataset (n = 416 228), individuals at higher predicted risk had higher long-term risk of heart failure (HR 12.54), aortic stenosis (HR 9.98), AF (HR 8·75), stroke/TIA (HR 8.07), CKD (HR 6.85), PVD (HR 6.62), valvular heart disease (HR 6.49), MI (HR 5.02), diabetes (HR 2.05) and COPD (HR 2.02) (Figure 1). This cohort were also at higher risk of death (HR 10.45), accounting for 74% of cardiovascular deaths (8 582 of 11 676) during 10-year follow up. Of 82 higher risk patients in the pilot study (mean age 71.6 years (SD 7.5), 50% women), the prevalence of cardio-renal-metabolic disease was high (Table 1), and there were opportunities to reduce future cardiovascular risk. Of higher risk patients with hypertension, 58.5% (31/53) of those aged <80 years had a systolic blood pressure (SBP)>140mmHg, and 54.5% (6/11) of those aged ≥80 years had a SBP >150mmHg. Of those with type 2 diabetes and co-existent ASCVD, only 23.1% (3/13) were on SGLT2 inhibitor therapy. Of higher risk patients on statin therapy, 37.0% (20/54) had LDL-cholesterol >1.8 mmol/L, and 52.0% (12/25) of patients with previous ASCVD had an LDL-cholesterol >1.4mmol/L. Furthermore, 19.5% (16/82) of the higher risk cohort had undiagnosed moderate or high risk CKD; who were infrequently prescribed a statin (41.7%; 5/12), ACE-i/ARB therapy with co-existent hypertension (61.5%. 8/13), or SGLT2 inhibitor with co-existent diabetes (83.3% (5/6)). Obesity was present in 49%, and 17% (14/82) were eligible for GLP-1 RA therapy. Conclusions The machine learning OPTIMISE algorithm can identify people at higher risk of cardio-renal-metabolic diseases and death using routinely collected data. On prospective evaluation higher risk individuals have unrecorded and undertreated cardio-renal-metabolic diseases, which are actionable targets for preventative care.Figure 1

Effect of a cardiovascular post discharge sms support program on healthcare utilisation - the hearthealth program

Abstract Background Cardiovascular disease (CVD) is a leading cause of mortality worldwide[1]. Targeting modifiable risk factors is key to primary and secondary prevention of CVD but many barriers to good risk factor control exist[2]. SMS message programs have shown to be an efficient modality to deliver information to improve knowledge and risk factor profiles for CVD patients[3]; however, their impact on healthcare utilisation has not been thoroughly examined. The HeartHealth program is a text message post-discharge support program delivered to CVD patients. It comprised regular semi-personalised text messages providing CVD information, advice, and support to patients over a 6-month period. Purpose This study aimed to examine the impact of the Heart Health program on healthcare service utilisation. Methods Patients ≥18 years old who recently attended cardiology clinics or were discharged from a cardiology unit, between April 2020 and April 2022 were invited to the program. We compared healthcare utilisation rates in patients who enrolled into the HeartHealth text program (intervention group) to contemporaneous patients who did not enrol in the program (control group). The primary outcome was the incidence rate of all-cause healthcare utilisation events (composite of ED presentations and/or hospital admissions for any medical cause) in the 6 months post-discharge. The secondary outcomes were incidence rates of CVD events and unplanned CVD events. All analyses were adjusted for demographic and co-morbidity variables. Results 11542 patients were included in analysis (intervention: 4324, control: 7218), mean age 58.8 years, 60.7% were male, and 78.3% with English as their preferred language. HeartHealth Intervention participants had lower rates of the primary outcome of healthcare service events compared to control participants (mean number of events 0.43 intervention vs 0.52 control, adjusted rate ratio [RR], 0.91 [95% CI, 0.83-0.99], p=0.033, Table 1). The intervention was significantly more effective in older patients compared to younger patients (RR, 0.82, [95% CI, 0.72-0.93] in patients aged ≥65 years, compared to patients <65 years, RR, 0.98, [95% CI, 0.87-1.10]; p-value for interaction =0.043, Figure 1). The subset of CVD events and unplanned CVD events were numerically lowering in the intervention group compared to the control, but the risk ratio not statistically significantly different in adjusted models (Table 1). Conclusion This analysis demonstrates that a text message post-discharge support program for CVD patients decreased the need for healthcare service utilisation for all medical causes. Future randomised controlled trials are required to further support these findings.Figure 1:Adjusted interaction analysisTable 1:Adjusted Incidence of events

Prevalence and incidence of chronic wounds in Austria - a population-based real-world data analysis

Abstract Background Chronic wounds are associated with pain, odor, loss of mobility, an increased risk for infection and sepsis and a reduced quality of life. Treatment costs are rising due to the longevity of the population and increasing number of diabetes cases. For service planning in healthcare, it is thus necessary to describe patient characteristics and estimate the prevalence and incidence of chronic wounds. Currently, no data exists on this subject broken down by age group, gender, and province in Austria. Methods A retrospective analysis of real-world data was conducted using two merged datasets from an outpatient wound centre and the Austrian Health Insurance Fund. The study population consisted of people who resided in Austria and were covered by statutory health insurance from 2018 to 2022. We performed a descriptive, socio-demographic analysis of the data of patients, followed by a set of cluster analyses using the unsupervised K-means algorithm. From these clusters, we derived subgroup characteristics and patient trajectories and calculated prevalence and incidence rates for chronic wounds according to diagnoses, different age groups, gender, and different regions. Results Gender was almost evenly distributed in the wound centre’s data set (n = 4963; 49.6% female). The age distribution revealed the age group from 71-80 years being the largest group. In general, more women than men are affected by chronic wounds from the age of 81 onwards. 31% of chronic wound patients had diabetes as an underlying condition. More men were affected by peripheral arterial occlusive disease and diabetic foot syndrome and, conversely, more women by chronic venous insufficiency. These are preliminary results of the analyses. Conclusions Chronic wound patients were characterised by older age and multi-morbidity. Interestingly, gender differences appeared in the occurrence of comorbidities. Key messages • This study makes a crucial contribution in making routine data usable for the epidemiological study of chronic wounds, a cluster of diseases of complex aetiology. • It thus contributes to filling a knowledge gap. The prevalence estimate serves as a basis of knowledge for health care planning and a basis for the health economic assessment of the problem.

Health impact of the Serious Accidents Punishment Act in Korean occupational settings

Abstract Background Interrupted time series analysis serves as a valuable study design for assessing the efficacy of public health interventions implemented at a specific moment in time at the population level. We aim to elucidate the effects of the Serious Accidents Punishment Act implemented in February 2021 in Korea by analyzing changes in the incidence rates of occupational diseases. Methods The monthly data from patients with occupational diseases was extracted from the National Health Insurance Service Cohort database from 2011 to 2023. An Interrupted time series analysis with Poisson segmented regression was used to compare the rates before and after the Serious Accidents Punishment Act introduction in both outpatients and inpatients. Adjustments or stratification variables included sex, age, company size, and injury-related international classification of diseases codes (Injury, poisoning, and certain other consequences of external causes, S00-T88). Results Based on injury rates, men’s inpatient injury rates remained stable, but outpatient rates decreased after the act implementation, while women’s injury rates consistently declined in both inpatient and outpatient settings. The Interrupted time series regression analysis indicates that the Serious Accidents Punishment Act led to a significant reduction in both outpatient and inpatient injury rates for men and women, with a marked decline in outpatient rates and hospital admissions among women post-intervention. Conclusions The Interrupted time series regression results suggest that the Serious Accidents Punishment Act has been effective in reducing injury-related healthcare usage, highlighting the necessity of gender-specific interventions and the potential impact on lowering inpatient visits, although causality remains uncertain without further analysis. Key messages • The Serious Accidents Punishment Act significantly reduced occupational injury rates in Korea, especially among women, demonstrating effective public health intervention. • Interrupted time series analysis reveals Serious Accidents Punishment Act’s impact on reducing healthcare usage for occupational injuries, highlighting the need for gender-specific approaches.

Interplay between family History and polygenic risk for coronary heart disease: a cohort study among over 60 thousand individuals

Abstract Background The degree to which background genetic risk adds to self-report of family history of coronary heart disease (CHD) remains an important question. Methods We utilized data from the multiethnic Genetic Epidemiology Resource in Adult Health and Aging (GERA) cohort of 60,070 Kaiser Permanente of Northern California (KPNC) members (mean ± SD age=59 ± 9 years; 67% female; 18% non-white). We characterized the cohort at baseline in 2003-2007. Excluding those with missing self-report of family history of CHD (n=1,718) resulted in a final sample of 61,352. We stratified the cohort into not having (n=42,866; 70%) and having (n=18,486; 30%) self-reported family history of CHD and then (within stratum of family history of CHD) by three groups of CHD polygenic risk (low: quintile 1; intermediate: quintiles 2, 3 and 4 combined; and high: quintile 5) using a validated 12-SNP polygenic risk score (PRS) for CHD (CARDIO inCode-Score®). Incident CHD was based on ICD-9/10 codes for angina pectoris, myocardial infarction, revascularization procedures or CHD death (n=3,040) through 12/31/2022; mean follow-up was 14.5 years. Results Age-adjusted CHD incidence rates per 10,000 person years were estimated using Poisson regression (accounting for death and health plan disenrollment) by absence/presence of family history of CHD and polygenic risk groups. As shown in the Figure, polygenic risk provided additional risk stratification within categories of family history. The hazard ratio of high PRS (vs low PRS) adjusted for age, sex, 10 principal components of ancestry, smoking, body mass index, diabetes, hypertension, total cholesterol/HDL ratio and cholesterol lowering therapy was 1.62 (95% CI, 1.39-1.87; p<0.001) in those with no family history of CHD, and 1.66 (95% CI, 1.37-2.00; p<0.001) in those with family history of CHD (p-interaction PRS continuous*family history of CHD=0.93). Conclusions Our results show that polygenic risk predicts future CHD regardless of the presence of family history of CHD. Thus, it is not enough to rely of family history to fully characterize potential genetic burden. These data are therefore important for the future of precision medicine.

How much does elective cardioversion increase the risk of ischaemic stroke compared to the baseline risk in atrial fibrillation? A nationwide study

Abstract Background Patients with atrial fibrillation (AF) undergoing cardioversion (CV) are exposed to an increased risk for stroke during the post-cardioversion period, but the exact magnitude of this risk after elective CV with preceding appropriate oral anticoagulant (OAC) therapy is unknown. Purpose We explored the rate of ischaemic stroke (IS) after elective CV and compared the IS rate during the post-cardioversion period with the long-term stroke rate in patients with AF using guideline-recommended OAC therapy. Methods This is a nationwide register-based study, including all AF patients undergoing their first-ever elective CV between 2012-18 in Finland. Data were collected from the Finnish health care registers covering uniquely all levels of care. Visual assessment of the survival curve identified a cut-off point in IS rate at 1 week after CV. Therefore, the follow-up time was split into two intervals, the 1-week post-cardioversion period and the subsequent period up to 360 days. Stroke rates were calculated separately for these periods. Unadjusted and adjusted incidence rate ratios were estimated with Poisson regression. Moreover, interaction between the two follow-up periods and conventional IS risk factors as well as OAC treatment was assessed. Results A total of 9625 AF patients undergoing their first elective CV were identified (mean age 67.7±9.9 years, 61.2% men, mean CHA2DS2-VASc score 2.6±1.6). Warfarin was used in 6 245 (64.9%) and non-vitamin K oral anticoagulants in 3 380 (35.1%) patients. Overall, 92 (1.0%) patients suffered an IS during the year after CV. The survival plot displayed a higher incidence of IS within the first week after CV, stabilizing thereafter to a consistent level (Figure). In the adjusted regression analyses, IS rate within the first week after elective CV was 13.6-fold (95% confidence interval [CI]: 8.6-21.5) compared the subsequent rate of IS (Table). We observed no significant interaction between any of the conventional IS risk factors or OAC treatment and the two follow-up time periods, indicating that their association with IS rate did not differ during the post-cardioversion period compared to the subsequent time period. Conclusions In this nationwide study, the rate of IS was roughly 14 times higher during the first week after elective CV compared to the subsequent follow-up time.Cumulative risk of IS after elective CVIncidence rates of IS after elective CV

Left ventricular ejection fraction and clinical outcomes after transcatheter aortic valve implantation

Abstract Background Reduced left ventricular ejection fraction (LVEF ≤50%) has been associated with poor prognosis in patients with severe aortic stenosis treated medically or with aortic valve replacement. However, less is known regarding the impact of different degrees of LVEF including moderately to severely reduced LVEF after transcatheter aortic valve replacement (TAVR). Purpose To examine the association between baseline LVEF and clinical outcomes after TAVR. Methods Patients undergoing TAVR between 2008-2021 from the Swedish Transcatheter Cardiac Intervention Registry (SWENTRY) were included. LVEF was estimated from echocardiography before TAVR and categorized as ≥50%, 40-49%, 30-39% and <30%. SWENTRY was linked to the National Patient Registry and Cause of Death Registry for outcome variables. Patients were followed for a median of 3.2 years for the primary outcome heart failure hospitalizations and the secondary outcome all-cause mortality. Cox regression analyses adjusted for age, sex, BMI, atrial fibrillation, eGFR class, diabetes, hypertension, frailty, chronic pulmonary disease and coronary artery disease were performed for the association between LVEF groups and outcome. Results In total, 8686 patients were included (mean age 81 years, 47% female) of whom 5904 (68%) patients had LVEF ≥50%, 1342 (15%) had LVEF 40-49%, 906 (10%) had LVEF 30-39% and 534 (6%) had LVEF <30%. Significant differences were observed across the LVEF groups in the cumulative incidence rates of heart failure hospitalizations (19, 30, 37 and 43%; p<0.001) and all-cause mortality (41, 54, 55, 57%; p<0.001) at five years. In adjusted analyses there was a stepwise increase in the risks of heart failure hospitalizations (Figure 1A) and all-cause mortality (Figure 1B) for each respective LVEF category. Conclusion Reduced LVEF, especially LVEF <30%, was associated with a dramatically increased long-term risk of heart failure hospitalizations and all-cause mortality in patients undergoing TAVR. LVEF should be considered in risk stratification and patient selection for TAVR.

Social vulnerability and disparities in incidence of diagnosed diabetes in the united states, 2004 to 2019

Abstract Introduction Vulnerable populations experience a higher burden of cardiovascular disease.(1) However, the incidence of cardiovascular risk factors, such as diabetes, within these populations, is incompletely characterized. Recently, the United States Centers for Disease Control and Prevention (US CDC) developed the Social Vulnerability Index (SVI) to categorize counties that may be vulnerable to worse health outcomes. The SVI is composed of 4 themes: socioeconomic status (Theme 1), household composition & disability (Theme 2), minority status & language (Theme 3), and housing type & transportation (Theme 4).(2) We sought to evaluate the association of the 4 SVI themes with county incidence of diagnosed diabetes. Method We used CDC data (2004-2019; reported for 94% of US counties), on county incidence of diagnosed diabetes. The SVI themes were scored from 0 to 1 (low to high vulnerability) based on national percentile ranking. We used weighted least squares regression with restricted cubic splines to model the relationship between SVI themes and incidence of diagnosed diabetes (median data 2004−2019), adjusting for median age, sex ratio, state, percent uninsured, food environment index, healthcare providers, and rurality.(3) The partial effects of SVI themes and diabetes incidence were reported as F-statistics (P-values) and diabetes incidence rate ratios (IRR [95% confidence interval]), which were plotted for all values compared with the 50th percentile (SVI 0.5). For each theme, we also present the IRR for a 0.5-point increase when moving over the lower (SVI score 0.5 vs. 0.0) and the upper (1.0 vs. 0.5) half of the SVI score distribution. Results The 4 SVI theme rank scores were significantly associated with diabetes incidence (all, P<.001). However, Theme 1 and 2 scores showed stronger associations with IRR than Theme 3 and 4 (Figure). For Theme 1, SVI score 0.5 vs. 0.0 was associated with a 15% higher incidence (IRR 1.15 [1.13–1.18]) and score 1.0 vs. 0.5 was associated with a 13% higher incidence (IRR 1.13 [1.11–1.16]). For Theme 2, SVI score 0.5 vs. 0.0 was associated with a 16% higher incidence (IRR 1.16 [1.14–1.18]), but there was no difference between rates for SVI score 1.0 vs. 0.5 (IRR 1.01 [0.99–1.03]). For Theme 3, there was no difference between SVI score 0.5 vs. 0.0 (IRR 0.98 [0.96–1.00]), but rates were 8% lower for SVI score 1.0 vs. 0.5 (IRR 0.92 [0.90–0.94]). For Theme 4, SVI score 0.5 vs. 0.0 was associated with a 3% lower incidence (IRR 0.97 [0.96–0.99]) and score 1.0 vs. 0.5 was associated with a 2% higher incidence (IRR 1.02 [1.01–1.04]). Conclusion In US counties, the strength and directionality of the association between SVI themes and diabetes incidence differed by theme and level of SVI scores. These themes, particularly socioeconomic status and household composition & disability may be leveraged to identify high-risk counties for primary prevention of diabetes, with implications for reduction in cardiovascular risk.

Cardiovascular events risk in office-masked nocturnal hypertension defined by home blood pressure monitoring: the J-HOP nocturnal blood pressure study

Abstract Background Elevated nocturnal home blood pressure (BP) has been reported to be associated with increased risk for cardiovascular disease (CVD). Masked hypertension defined by home BP monitoring is also a strong risk factor for adverse CVD outcomes. However, no study has investigated the association between office-masked nocturnal hypertension defined by home BP monitoring and CVD events risk. Purpose This study aimed to examine the association between office-masked nocturnal hypertension defined by home BP monitoring and CVD events risk in a clinical practice-based population. Methods This was a prospective observational study including Japanese participants with CVD or high risk of CVD. Three office BPs were taken on two different occasions. Nocturnal home BP was measured three times per night for two weeks. The association between office-masked nocturnal hypertension and incident total CVD events (including fatal and non-fatal stroke and coronary heart disease) was examined using Cox regression. Results 2,545 participants were followed for the mean of 7.1 years (18,116 person-years), during which 152 (6.0%) CVD events occurred. Mean age (standard deviation) was 63.3 (10.3) years; 49.0% were male; 82.6% took antihypertensive medications. The proportions of participants with normotension (office BP <140/90 mmHg and nocturnal home BP <120/70 mmHg), white-coat hypertension (office BP ≥140/90 mmHg and nocturnal home BP <120/70 mmHg), office-masked nocturnal hypertension (office BP <140/90 mmHg and nocturnal home BP ≥120/70 mmHg), and sustained hypertension (office BP ≥140/90 mmHg and nocturnal home BP ≥120/70 mmHg) were 25.3%, 14.4%, 23.2%, and 37.1%, respectively. The office-masked nocturnal hypertensive group and sustained hypertensive group had higher incidence rates of total CVD events compared with the normotensive group. Relative to normotension, those with both office-masked nocturnal hypertension (adjusted hazard ratio [aHR] 1.72, 95% confidence interval [CI] 1.01–2.92) and sustained hypertension (aHR 1.75, 95%CI 1.03–2.96) had similarly increased CVD risk, even after adjustment for daytime home BP values. Conclusions Screening for office-masked nocturnal hypertension with home BP monitoring identifies a potentially important group of patients with increased risk for incident CVD events for whom additional preventative measures may be appropriate.

Burden and sociodemographic disparities in cardiovascular mortality rates associated with hypercholesterolemia in united states: a nationwide county-level analysis from 2010 to 2019

Abstract Background Hypercholesterolemia (HC), a major public health concern, has seen a rising prevalence in US adults and globally, leading to increased morbidity and mortality. Despite well-established links between HC and cardiovascular mortality (CVM), the specific impacts and disparities at the population level remain poorly understood. Purpose This study aims to assess the independent effects of HC on VM across the overall US population, examining variations across sociodemographic groups and geographic locations. Methods Age-adjusted county-level CV rates (ACVM per 100,000 individuals) between 2010 to 2019 were obtained using the Center for Disease Control and Prevention (CDC) database. Using the CDC surveillance system, HC rates per county were assessed as the proportion of adults (+18) with high total blood cholesterol. County health ranking project databases were utilized to acquire county characteristics and demographics. Poison generalized estimating equation models were employed to assess incidence rate ratios (IRR). Results Of 307,045,656 residents who lived in 3142 US counties in 2010, a total of 8,157,580 (2.7%) CV deaths occurred between 2010-2019. In a fully adjusted model*, high HC rates associated with high ACVM (Standardized IRR: 1.049; Figure 1). In subgroup analyses, HC rates associated with a greater ACVM among counties with high minority (IRR: 1.070) versus low (IRR: 1.043), and in rural areas (IRR: 1.052) versus urban (IRR: 1.041). Notably, this association was prominent in areas with high poverty (Q4 vs. Q1) (IRR: 1.062 vs. 1.035; p interaction <0.001; Figure 1). Further, higher ACVM rates related to HC were observed in the South and Northeast U.S. regions. Conclusions HC rates are independently associated with high ACVM across most sociodemographic groups and locations, with the most pronounced effect in areas with high poverty levels and minority populations. These findings call on targeted interventions and policymaking aimed at mitigating the prevalence of HC and cardiovascular burden, particularly in vulnerable populations.

Electronic consultation from primary care to a cardiology department improves outcomes in patients with cancer

Abstract Background The number of cancer patients with known cardiovascular (CV) disease is increasing due to improved cancer prognosis. Purpose The objective of this study is to assess the long-term results of cancer patients referred to a cardiology department by primary care using electronic consultation (e-consultation). Methods We analysed the patients with previous diagnosis of cancer referred to a cardiology department (CD) from 2010 to 2021 (n=6.889), selected from a total of 68.518 patients (61.629 without cancer), and compared two assistance models: in-person practice (from 2010 to 2012) and e-consultation (from 2013 to 2021). In the first period, all the patients referred by primary care physicians (PCPs) were seen in an in-person consultation and in the e-consultation model the cardiologist reviewed the electronic records (e-consultation) and decided to solve without any visit or, if it was necessary, with an in-person consultation. The outcomes between both periods were analysed using an interrupted time series regression model: 1) delay time to cardiology assistance; 2) all-cause and cardiovascular hospital admissions, and 3) all-cause and cardiovascular mortality during the first year after the initial consultation or e-consultation to the CD. Results Among cancer patients referred to cardiology consultation, the introduction of e-consultation decreased waiting times to cardiology care by 51,8% (95% CI: 51,7%-51,9%) (Fig 1). Over 60% of referrals were resolved in less than 8 days, with this proportion significantly higher after the e-consultation program was introduced (p<0,001). Furthermore, we observed a reduction in the one-year rate of outcomes, with an incidence rate ratio (iRR) [IC 95%] of 0,75 [0,73-0,77] for CV-related hospitalizations (Fig 2b), 0,43 [0,42-0,44] for all-cause hospitalization (Fig 2a), and 0,87 [0,86-0,88] for all-cause mortality. In the multivariate analysis, the delay in receiving cardiology care was significantly associated with an independent increase in 1-year mortality (OR [95% CI] 1,39 [1,06-1,83]) and hospital admission (OR [95% CI] 1,25 [1,02-1,52]). Furthermore, the implementation of the e-consult model was associated with a reduction in hospital admission rates (OR [95% CI] 0,19 [0,14-0,25]). Conclusions In comparison to the in-person consultation period, an outpatient care program that incorporates e-consultation for cancer patients significantly reduced waiting times for cardiology care and shown to be safe, associated with lower rates of hospital admissions.Figure 1Figure 2

Impact of agitation status during intensive care on functional outcomes and mortality in patients with cardiovascular disease

Abstract Background Agitation in patients during intensive care is a frequent complication. Several studies have reported that restlessness and agitation are risk factors for prolonged intensive care unit (ICU) stay and poor prognosis. Since patients with cardiovascular disease (CVD) requiring intensive care are ageing and thereby easily affected by responses, including changes in mental status, optimal management of sedation and agitation statuses during ICU stay is considered crucial. However, the influence of different agitation levels during CVD treatment in the ICU on clinical outcomes after ICU discharge is still unclear. Purpose To investigate the associations of the agitation level during ICU stay with mortality after ICU admission and functional outcomes at hospital discharge. Methods We studied 2236 patients (mean age 67.8±0.3 years) who were admitted to the ICU of a university hospital for CVD treatment and whose highest Richmond Agitation-Sedation Scale (RASS) ≥0, measured daily during ICU stay. In addition to clinical characteristics, we investigated the incidence of all-cause mortality during hospitalization and after hospital discharge. We also measured functional outcomes at discharge among 1625 patients, including 6 minutes walk distance (6MWD), Mini-Cog test, and Patient Health Questionnaire-2 (PHQ-2) as physical, cognitive, and mental functions, respectively. In statistical analysis, patients were divided into three groups based on the highest RASS levels during ICU stay in each patient (Calm: RASS=0, Restless: RASS=1, Agitation: RASS≥2). Kaplan-Meier analysis with a log-rank test and the multivariate Cox proportional hazard model were used to clarify whether higher agitation levels were associated with all-cause mortality. Moreover, the differences between the agitation levels and functional outcomes at hospital discharge were compared using the analysis of covariance. Results During the median follow-up of 1.9 years, all-cause death occurred in 280 patients (12.5%), with an incidence rate of 5.57/100 person-years. The Restless and Agitation groups showed higher mortality than the Calm group (P<0.001), and higher agitation levels in the ICU were significantly associated with a higher rate of all-cause mortality (adjusted hazard ratio: 1.37, 95% confidence interval: 1.19–1.57, P<0.001). Furthermore, as compared with the Calm group, the Restless and Agitation groups showed significantly lower levels of 6MWD (all P<0.001) and Mini-cog (P=0.004 and P<0.001, respectively) and a higher PHQ-2 (all P<0.001), even after adjusting for clinical confounders. Conclusions Agitation during ICU stay in CVD patients was associated with low functional outcomes at hospital discharge and high mortality rate after discharge, irrespective of agitation level. Detailed information on the agitation status during intensive care may be an important indicator in developing management and treatment strategies for patients with CVD admitted to ICU.

Comprehensive analysis of clinical features, mRNA splicing, and immunological role of REEP5 in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is a prevalent malignancy within the digestive system, characterized by high incidence and mortality rates. The biological role of REEP5 in ESCC progression remains poorly understood, despite its associations with various diseases, potentially accelerating tumor malignancy. We retrieved RNA-seq data and clinical information from 179 ESCC patients from the Gene Expression Omnibus (GEO) and 93 patients from The Cancer Genome Atlas (TCGA) databases. Bioinformatics analyses were conducted to explore the biological functions of REEP5 in ESCC, its role in the tumor microenvironment, and its prognostic value. Additionally, utilizing single-cell RNA-seq (scRNA-seq) data from 3 ESCC patients in the GEO database, we performed cluster analyses to investigate cell-specific expression differences of REEP5 between cancerous and adjacent non-cancerous tissues. Molecular biology experiments were also conducted to validate REEP5 expression disparities between tumor and non-tumor tissues. Compared to normal tissues, REEP5 was significantly enriched in ESCC tissues. High REEP5 expression was closely associated with poor prognosis in ESCC patients. Gene Ontology (GO) analysis revealed strong correlations between REEP5 and processes such as mRNA splicing and protein stabilization. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) indicated positive correlations between REEP5 and mRNA spliceosome assembly and disassembly. Pearson correlation analysis demonstrated positive associations between REEP5 and cancer-inhibitory immune checkpoints CTLA-4, TIM-3, and HVEM. Single-cell clustering and CIBERSORT analysis showed that REEP5 expression was closely related to T-cell infiltration in ESCC, with significant enrichment effects observed in CD8+ T-cell infiltration. REEP5 expression is closely correlated with the pathological and molecular pathology of ESCC, potentially playing a crucial role in Mast cell or T-cell-mediated immune responses in ESCC. Therefore, REEP5 holds promise as a novel therapeutic target for ESCC.

Deep Learning With Optical Coherence Tomography for Melanoma Identification and Risk Prediction.

Malignant melanoma is the most severe skin cancer with a rising incidence rate. Several noninvasive image techniques and computer-aided diagnosis systems have been developed to help find melanoma in its early stages. However, most previous research utilized dermoscopic images to build a diagnosis model, and only a few used prospective datasets. This study develops and evaluates a convolutional neural network (CNN) for melanoma identification and risk prediction using optical coherence tomography (OCT) imaging of mice skin. Longitudinal tests are performed on four animal models: melanoma mice, dysplastic nevus mice, and their respective controls. The CNN classifies melanoma and healthy tissues with high sensitivity (0.99) and specificity (0.98) and also assigns a risk score to each image based on the probability of melanoma presence, which may facilitate early diagnosis and management of melanoma in clinical settings.

Temporal trends of thyroid cancer in China and globally from 1990 to 2021: an analysis of the global burden of Disease Study 2021

The incidence of thyroid cancer (TC) is increasing annually worldwide, with a growing burden. This study aims to analyze temporal trends in the burden of TC by age and sex in China and globally from 1990 to 2021, including incidence, prevalence, mortality, and disability-adjusted life years (DALYs) rates, and to predict future trends. We obtained data on TC in China and globally from 1990 to 2021 from the Global Burden of Disease (GBD) database. Using the Joinpoint regression model, we calculated and analyzed the trends in age-standardized incidence rate (ASIR), age-standardized prevalence rate (ASPR), age-standardized mortality rate (ASMR), and age-standardized DALYs rate (ASDR). Specifically, we estimated the annual percent change (APC), the average annual percent change (AAPC), and the corresponding 95% confidence intervals (95% CI) for each metric. Additionally, we conducted a decomposition analysis to investigate the impact of aging, population growth, and epidemiological factors on the incidence and mortality rates of TC. Furthermore, the autoregressive integrated moving average (ARIMA) model was employed to predict the burden of TC from 2022 to 2036. From 1990 to 2021, the ASIR for TC in China increased from 1.249 (95% uncertainty interval [UI]: 1.009–1.473) per 100,000 to 2.473 (95% UI: 1.993–3.088) per 100,000. Conversely, the ASMR decreased from 0.473 (95% UI: 0.403–0.550) per 100,000 to 0.387 (95% UI: 0.307–0.472) per 100,000. Both males and females demonstrated an upward trajectory in ASIR. However, while the ASMR for females decreased, that for males showed an overall increase despite a decline in the last decade. The age of peak onset for TC ranged from 30 to 79 years, whereas the age of peak mortality was between 50 and 89 years. The analysis using the AAPC indicates that the growth in the ASIR (AAPC = 2.242, 95% CI: 2.112–2.371) and ASPR (AAPC = 2.975, 95% CI: 2.833–3.117) in China exceeds the global rate. Furthermore, the reduction in ASMR (AAPC = -0.651, 95% CI: -0.824 - -0.479) and ASDR (AAPC = -0.590, 95% CI: -0.787 - -0.392) in China is also more pronounced than globally. Decomposition analysis indicates that the increasing TC burden in China is primarily driven by population aging, whereas globally, population growth plays a more significant role. Projections based on predictive models suggest that from 2021 to 2036, the ASIR for both China and the global population is expected to continue rising, while the ASMR is anticipated to decline further. The incidence rates of TC in China and globally have shown a continuous upward trend, which is expected to persist over the next 15 years. Additionally, although the number of male TC cases is relatively lower compared to females, the overall ASMR and ASDR for males have shown an upward trend, despite a slight decline in recent years. This highlights the need to enhance prevention, diagnosis, and treatment measures, and to develop differentiated screening and treatment strategies based on age and sex.

Virologically suppressed switch to Dolutegravir/Lamivudine 2-Drug regimen versus switch to commonly prescribed 3-Drug regimens in the United States

BackgroundTwo-drug regimens (2DRs) have been introduced in recent years to potentially reduce antiretroviral therapy (ART) toxicities and drug-drug interactions while demonstrating comparable efficacy to three-drug regimens (3DRs) for people with HIV (PWH). The objective of this study was to compare the real-world effectiveness and durability of a single-tablet 2DR of dolutegravir/lamivudine (DTG/3TC) with that of commonly prescribed 3DRs in ART-experienced, virologically suppressed PWH during the first 24 months of DTG/3TC availability in the United States.MethodsVirologically suppressed (viral load [VL] < 200 copies/mL) adult PWH initiating DTG/3TC 2DR, bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF), or a DTG-based 3DR between 01MAY2019 and 31OCT2020 were identified in the OPERA® cohort and followed through 30APR2021. Univariate Poisson regression (incidence rates) and marginal structural Cox proportional hazards models with inverse probability of treatment weights (hazard ratios) were used to quantify relationships between regimen type and confirmed virologic failure (2 consecutive VLs ≥ 200 copies/mL) or regimen discontinuation. Reasons for discontinuation were examined.ResultsA total of 8,037 ART-experienced, virologically suppressed PWH met the inclusion criteria and switched to DTG/3TC (n = 1,450), BIC/FTC/TAF (n = 5,691), or a DTG-based 3DR (n = 896). Incidence rates of confirmed virologic failure were low for all groups, at 0.66 (DTG/3TC), 0.84 (BIC/FTC/TAF), and 1.78 (DTG 3DR) per 100 person-years (py). Compared to DTG/3TC, only the DTG 3DRs were associated with a statistically significant increased hazard of confirmed virologic failure (hazard ratio: 5.21, 95% confidence interval: 1.85, 14.67). Discontinuation rates per 100 py were highest in the DTG 3DR group (24.90), followed by the DTG/3TC group (17.69) and the BIC/FTC/TAF group (8.30). Regardless of regimen, discontinuations were infrequently attributed to effectiveness (VL ≥ 200 copies/mL; 4%) or tolerability (adverse diagnoses, side effects, or lab abnormalities; 6%).ConclusionsAmong virologically suppressed PWH initiating a new regimen, few individuals experienced virologic failure in real-world clinical care. While rates of regimen discontinuation were high, most discontinuations could not be attributed to a lack of virologic control or poor tolerability. These findings suggest that DTG/3TC is an effective option for ART-experienced, virologically suppressed PWH.

Novel Perspectives in the Management of Colorectal Cancer: Mechanistic Investigations Into the Reversal of Drug Resistance via Active Constituents Derived From Herbal Medicine.

The high incidence and mortality rate of colorectal cancer have become a significant global health burden. Chemotherapy has been the traditional treatment for colorectal cancer and has demonstrated promising antitumor effects, leading to significant improvements in patient survival. However, the development of chemoresistance poses a major challenge during chemotherapy in colorectal cancer, significantly impeding treatment efficacy and affecting patient prognosis. Despite the development of a variety of novel anticolorectal cancer chemotherapy agents, their effectiveness and side effects vary, possibly due to the complex mechanisms of resistance in colorectal cancer. Abnormal drug metabolism or protein targets are the most direct causes of resistance. Further studies have revealed that these resistance mechanisms involve biochemical processes such as altered protein expression, autophagy, and epithelial-mesenchymal transitions. Herbal active ingredients offer an alternative treatment option and have shown promise in reversing colorectal cancer drug resistance. This paper aims to summarize the role of various biochemical processes and key protein targets in the occurrence and maintenance of resistance mechanisms in colorectal cancer. Additionally, it elaborates on the mechanisms of action of herbal active ingredients in reversing colorectal cancer drug resistance. The article also discusses the limitations and opportunities in developing novel anticolorectal cancer drugs based on herbal medicine.

Curcumin Administration Routes in Breast Cancer Treatment

Breast cancer is a public health concern worldwide, characterized by increasing incidence and mortality rates, requiring novel and effective therapeutic strategies. Curcumin is a bioactive compound extracted from turmeric with several pharmacological activities. Curcumin is a multifaceted anticancer agent through mechanisms including the modulation of signaling pathways, inhibition of cell proliferation, induction of apoptosis, and production of reactive oxygen species. However, the poor water solubility and bioavailability of curcumin create important barriers in its clinical application. This review elaborates on the therapeutic potential of curcumin in breast cancer treatment, focusing on the efficacy of different administration routes and synergistic effects with other therapeutic agents. The intravenous administration of curcumin-loaded nanoparticles significantly improves bioavailability and therapeutic outcomes compared to oral routes. Innovative formulations, such as nano-emulsifying drug delivery systems, have shown promise in enhancing oral bioavailability. While intravenous delivery ensures higher bioavailability and direct action on tumor cells, it is more invasive and expensive than oral administration. Advancing research on curcumin in breast cancer treatment is essential for improving therapeutic outcomes and enhancing the quality of life of patients.

Knee joint dislocations-Current epidemiology and treatment in Germany.

Knee joint dislocations, though rare, present significant challenges due to potential complications like vascular and nerve damage, and are known to be often linked to sports injuries, accidents and obesity. This study aims to analyse the epidemiology, incidence and treatment approaches for knee dislocations in Germany from 2019 to 2022. This retrospective cohort study utilized data from the German Institute for the Hospital Remuneration System to examine knee dislocation cases across German medical institutions. Patient data coded under International Statistical Classification of Diseases and Related Health Problems 10 for 'knee dislocation' enabled detailed analysis by age, sex and surgical procedures categorized by operation and procedure codes. The Patient Clinical Complexity Level (PCCL) assessed complication severity. Analysis of 1643 knee dislocation cases revealed an incidence rate of 0.44-0.54 per 100,000 inhabitants annually. During the years 2020 and 2021, there were fewer cases of knee dislocations. Male patients comprised 50%-56% of cases, with an average hospital stay of 11 days. Most cases were PCCL 0 (62%-72%) and predominantly affected patients aged 18-29 years. Anterior tibial dislocations were common among classified cases. Injuries included ligament ruptures, meniscus lesions and grade I soft-tissue injuries. Patients with pre-existing knee prostheses constituted 0%-16% annually. Treatment involved closed reduction, external fixation and surgeries like capsuloligamentous reconstructions and arthroscopic procedures. Revision knee arthroplasty was required in 2%-9% of cases, with obesity rates up to 7%. This study provides valuable insights into the epidemiology, incidence and treatment of knee dislocations in Germany, with a focus on demographic risk factors, treatment complexities and the impact of obesity and knee prostheses. The findings emphasize the importance of specialized care in larger hospitals, comprehensive management of concomitant injuries and the need for improved coding accuracy. Future research should aim to refine treatment protocols. Level III.

Forecasting the trend of tuberculosis incidence in Anhui Province based on machine learning optimization algorithm, 2013–2023

Tuberculosis has been one of the most common communicable diseases raising global concerns. Accurately predicting the incidence of Tuberculosis remains challenging. Here we constructed a time-series analysis and fusion tool using multi-source data, and aimed to more accurately predict the incidence trend of tuberculosis of Anhui Province from 2013 to 2023. Random forest algorithm (RF), Feature Recursive Elimination (RFE) and Least absolute shrinkage and selection operator (LASSO) were implemented to improve the derivation of features related to infectious diseases and feature work. Based on the characteristics of infectious disease data, a model of RF-RFE-LASSO integrated particle swarm optimization multiple inputs long short term memory recurrent neural network (RRL-PSO-MiLSTM) was created to perform more accurate prediction. Results showed that the PSO-MiLSTM achieved excellent prediction results compared with common single-input and multi-input time-series models (test set MSE:42.3555, MAE: 59.3333, RMSE: 146.7237, MAPE: 2.1133, R2: 0.8634). PSO-MiLSTM enriches and complements the methodological research content of calibrating the time-series predictive analysis of infectious diseases using multi-source data, and can be used as a brand-new benchmark for the analysis of influencing factors and trend prediction of infectious diseases at the public health level in the future, as well as providing a reference for incidence rate prediction of infectious diseases.