Risk Factor Profile Research Articles

A comprehensive dataset of annotated oral cavity images for diagnosis of oral cancer and oral potentially malignant disorders

ObjectivesThis study aims to address the critical gap of unavailability of publicly accessible oral cavity image datasets for developing machine learning (ML) and artificial intelligence (AI) technologies for the diagnosis and prognosis of oral cancer (OCA) and oral potentially malignant disorders (OPMD), with a particular focus on the high prevalence and delayed diagnosis in Asia. Materials and methodsFollowing ethical approval and informed written consent, images of the oral cavity were obtained from mobile phone cameras and clinical data was extracted from hospital records from patients attending to the Dental Teaching Hospital, Peradeniya, Sri Lanka. After data management and hosting, image categorization and annotations were done by clinicians using a custom-made software tool developed by the research team. ResultsA dataset comprising 3000 high-quality, anonymized images obtained from 714 patients were classified into four distinct categories: healthy, benign, OPMD, and OCA. Images were annotated with polygonal shaped oral cavity and lesion boundaries. Each image is accompanied by patient metadata, including age, sex, diagnosis, and risk factor profiles such as smoking, alcohol, and betel chewing habits. ConclusionResearchers can utilize the annotated images in the COCO format, along with the patients’ metadata, to enhance ML and AI algorithm development.

Coronary risk factor profiles according to different age categories in premature coronary artery disease patients who have undergone percutaneous coronary intervention

Many studies have investigated the coronary risk factors (CRFs) among premature coronary artery disease (PCAD) patients. However, reports on the proportion and CRFs of PCAD according to different age cut-offs for PCAD is globally under-reported. This study aimed to determine the proportion of PCAD patients and analyse the significant CRFs according to different age cut-offs among percutaneous coronary intervention (PCI)-treated patients. Patients who underwent PCI between 2007 and 2018 in two cardiology centres were included (n = 29,241) and were grouped into four age cut-off groups that defines PCAD: (A) Males/females: < 45, (B) Males: < 50; Females: < 55, (C) Males: < 55; Females: < 60 and (D) Males: < 55; Females: < 65 years old. The average proportion of PCAD was 28%; 9.2% for group (A), 21.5% for group (B), 38.6% and 41.9% for group (C) and (D), respectively. The top three CRFs of PCAD were LDL-c level, TC level and hypertension (HTN). Malay ethnicity, smoking, obesity, family history of PCAD, TC level and history of MI were the independent predictors of PCAD across all age groups. The proportion of PCAD in Malaysia is higher compared to other studies. The most significant risk factors of PCAD are LDL-c, TC levels and HTN. Early prevention, detection and management of the modifiable risk factors are highly warranted to prevent PCAD.

Characteristics and risk profiles of patients with pulmonary arterial or chronic thromboembolic pulmonary hypertension living permanently at >2500 m of high altitude in Ecuador.

Over 80 Mio people worldwide live >2500 m, including at least as many patients with pulmonary vascular disease (PVD), defined as pulmonary arterial or chronic thromboembolic pulmonary hypertension (PAH/CTEPH), as elsewhere (estimated 0.1‰). Whether PVD patients living at high altitude have altered disease characteristics due to hypobaric hypoxia is unknown. In a cross-sectional study conducted at the Hospital Carlos Andrade Marin in Quito, Ecuador, located at 2840 m, we included 36 outpatients with PAH or CTEPH visiting the clinic from January 2022 to July 2023. We collected data on diagnostic right heart catheterization, treatment, and risk factors, including NYHA functional class (FC), 6-min walk distance (6MWD), and NT-brain natriuretic peptide (BNP) at baseline and at last follow-up. Thirty-six PVD patients (83% women, 32 PAH, 4 CTEPH, mean ± SD age 44 ± 13 years, living altitude 2831 ± 58 m) were included and had the following baseline values: PaO2 8.2 ± 1.6 kPa, PaCO2 3.9 ± 0.5 kPa, SaO2 91 ± 3%, mean pulmonary artery pressure 53 ± 16 mmHg, pulmonary vascular resistance 16 ± 4 WU, 50% FC II, 50% FC III, 6MWD 472 ± 118 m, BNP 490 ± 823 ng/L. Patients were treated for 1628 ± 1186 days with sildenafil (100%), bosentan (33%), calcium channel blockers (33%), diuretics (69%), and oxygen (nocturnal 53%, daytime 11%). Values at last visit were: FC (II 75%, III 25%), 6MWD of 496 ± 108 m, BNP of 576 ± 5774 ng/L. Compared to European PVD registries, ambulatory PVD patients living >2500 m revealed similar blood gases and relatively low and stable risk factor profiles despite severe hemodynamic compromise, suggesting that favorable outcomes are achievable for altitude residents with PVD. Future studies should focus on long-term outcomes in PVD patients dwelling >2500 m.

Distinct genetic liability profiles define clinically relevant patient strata across common diseases

Stratified medicine holds great promise to tailor treatment to the needs of individual patients. While genetics holds great potential to aid patient stratification, it remains a major challenge to operationalize complex genetic risk factor profiles to deconstruct clinical heterogeneity. Contemporary approaches to this problem rely on polygenic risk scores (PRS), which provide only limited clinical utility and lack a clear biological foundation. To overcome these limitations, we develop the CASTom-iGEx approach to stratify individuals based on the aggregated impact of their genetic risk factor profiles on tissue specific gene expression levels. The paradigmatic application of this approach to coronary artery disease or schizophrenia patient cohorts identified diverse strata or biotypes. These biotypes are characterized by distinct endophenotype profiles as well as clinical parameters and are fundamentally distinct from PRS based groupings. In stark contrast to the latter, the CASTom-iGEx strategy discovers biologically meaningful and clinically actionable patient subgroups, where complex genetic liabilities are not randomly distributed across individuals but rather converge onto distinct disease relevant biological processes. These results support the notion of different patient biotypes characterized by partially distinct pathomechanisms. Thus, the universally applicable approach presented here has the potential to constitute an important component of future personalized medicine paradigms.

Assessment of Risk of Type 2 Diabetes using Indian Diabetes Risk Score: A Community-Based Cross-Sectional Study in Marathwada region of Maharashtra

Background: Diabetes mellitus is one of the non-communicable diseases which have become a major global health problem whose prevalence is increasing worldwide and will reach to 12.2% (783 million) by 2045. The risk of diabetes escalates with increase in the number of risk factors and their duration as well. The Indian Diabetic Risk Score (IDRS) is a simple, low cost, feasible tool for mass screening programme for diabetes at the community level. Hence the present study was carried out to assess the level of risk of developing type 2 diabetes using IDRS. Methods: A cross-sectional study was carried out amongst 380 participants aged 20 years and above during the period of July 2018 to June 2019 in the field practice area of Rural Health Training Centre of IIMSR Medical College in Jalna, Maharashtra. A semi-structured interview schedule consisting of socio-demographic characteristics, risk factor profile and Indian Diabetes Risk Score was used. Data was analysed by using appropriate statistical test whenever necessary. Results: In our study, 52% are moderately at risk and 2% are at high risk for developing diabetes mellitus. About 62.1% participants belonged to nuclear family, 42.6% had family history of diabetes mellitus, 76.3% carried out moderate physical activity and 50.3% were overweight / obese. Family history of diabetes, lack of physical activity and overweight / obesity were found to be potential risk factors for developing diabetes mellitus. Conclusion: More than half i.e. 52% of the study subjects were at risk of having diabetes, hence screening is of utmost importance so that interventions can be initiated at an early stage.

The profile of patients with postpartum hemorrhage admitted to the obstetric intensive care: a cross-sectional study.

In Brazil, postpartum hemorrhage (PPH) is a major cause of maternal morbidity and mortality. Data on the profile of women and risk factors associated with PPH are sparse. This study aimed to describe the profile and management of patients with PPH, and the association of risk factors for PPH with severe maternal outcomes (SMO). A cross-sectional study was conducted in Instituto de Medicina Integral Prof. Fernando Figueira (IMIP) obstetric intensive care unit (ICU) between January 2012 and March 2020, including patients who gave birth at the hospital and that were admitted with PPH to the ICU. The study included 358 patients, of whom 245 (68.4%) delivered in the IMIP maternity, and 113 (31.6%) in other maternity. The mean age of the patients was 26.7 years, with up to eight years of education (46.1%) and a mean of six prenatal care. Uterine atony (72.9%) was the most common cause, 1.6% estimated blood loss, 2% calculated shock index (SI), 63.9% of patients received hemotransfusion, and 27% underwent hysterectomy. 136 cases of SMO were identified, 35.5% were classified as maternal near miss and 3.0% maternal deaths. Multiparity was associated with SMO as an antepartum risk factor (RR=1.83, 95% CI1.42-2.36). Regarding intrapartum risk factors, abruptio placentae abruption was associated with SMO (RR=2.2 95% CI1.75-2.81). Among those who had hypertension (49.6%) there was a lower risk of developing SMO. The principal factors associated with poor maternal outcome were being multiparous and placental abruption.

Biomechanical and biological factors of sexual dimorphism in anterior knee pain: Current concepts

Female gender is one of the commonly mentioned risk factors for anterior knee pain (AKP), among a spectrum of other factors including anatomical, biomechanical, hormonal, behavioral and psychological elements contributing to its development. Despite the focus on individual risk factors, there's a notable gap in comprehending how gender influences and interacts with other risk factors. The objective of this review was to identify and emphasize the connections between these interactions, gender-related risk factors for AKP, and the potential mechanisms that explain their associations with other risk factors, aiming to aid in the creation of precise prevention and treatment approaches. Gender influences the majority of risk factors for AKP, including anatomical, biomechanical, hormonal, behavioral and psychological factors. Women have on average smaller patellae, higher patellofemoral cartilage stress and for AKP, disadvantageous trochlear morphology, ligament and muscle composition and unfavorable neuromuscular control pattern. In contrast, men show on average an increased ability to strengthen their hip external rotators, which are both protective against AKP. Particularly in kinetic and kinematic analysis, men have been shown to have a distinctly different risk factor profile than women. Sex hormones may also play a role in the risk of AKP, with estrogen potentially influencing ligamentous laxity, increasing midfoot loading and affecting neuromuscular control of the lower extremities and testosterone positively affecting muscle mass and strength. The higher incidence of AKP in women is likely due to a combination of slightly increased risk factors. Although all risk factors can be present in both men and women and the holistic evaluation of each individual's risk factor composition is imperative regardless of gender, knowing distinctive risk factors may help with focused evaluation, treatment and implementing preventive measures of AKP.

Factors associated with unintended pregnancy and contraceptive practices in justice-involved adolescent girls in Australia.

Despite a decline in unintended teenage pregnancy in Australia, rates remain higher amongst justice-involved adolescent girls, who are more likely to be from disadvantaged socio-economic backgrounds, have histories of abuse, substance use and/or mental health issues. Furthermore, exposure to the criminal justice system may alter access to education and employment and opportunities, potentially resulting in distinct risk-factor profiles. We examine factors associated with unintended pregnancy, non-contraceptive use and Long-Acting Reversible Contraception (LARC) in a sample of sexually active, justice-involved adolescent girls from Western Australia and Queensland. Data from the Mental Health, Sexual Health and Reproductive Health of Young People in Contact with the Criminal Justice System (MeH-JOSH) Study was analysed on 118 sexually active adolescent girls. Participants were aged between 14 and 17 years, purposefully sampled based on justice-system involvement and completed an anonymous telephone survey. We constructed two multivariate models taking reproductive outcomes as the dependent variables. Over one quarter (26%, 30/118) reported a past unintended pregnancy, 54 did not use any contraception at their last sexual encounter, and 17 reported LARC use. Following adjustments in the multivariate analysis, lifetime ecstasy use was associated with both unintended pregnancy (aOR 3.795, p = 0.022) and non-contraception use (aOR 4.562, p = 0.004). A history of physical abuse was also associated with both any contraception (aOR 3.024, p = 0.041) and LARC use (aOR 4.892, p = 0.050). Identifying as Aboriginal & Torres Strait Islander, education/employment status and geographic location appeared to have no association. Our findings suggest that justice-involved adolescent girls have distinct risk factors associated with unplanned pregnancy and contraception use compared to the general population, but more research is required to understand the mechanisms and contexts underlying these risk factors. How exposure to physical violence may encourage contraception and LARC use, in particular, warrants further attention as does the association with ecstasy use.

The epidemiology of behavioral risk factors for noncommunicable disease and hypertension: A cross-sectional study from Eastern Uganda.

In light of the suboptimal noncommunicable disease (NCD) risk factor surveillance efforts, the study's main objectives were to: (i) characterize the epidemiological profile of NCD risk factors; (ii) estimate the prevalence of hypertension; and (iii) identify factors associated with hypertension in a peri-urban and rural Ugandan population. A population-based cross-sectional survey of adults was conducted at the Iganga-Mayuge Health and Demographic Surveillance System site in eastern Uganda. After describing sociodemographic characteristics, the prevalence of NCD risk factors and hypertension was reported. Prevalence ratios for NCD risk factors were calculated using weighted Poisson regression to identify factors associated with hypertension. Among 3220 surveyed respondents (mean age: 35.3 years (standard error: 0.1), 49.4% males), 4.4% were current tobacco users, 7.7% were current drinkers, 98.5% had low fruit and vegetable consumption, 26.9% were overweight, and 9.3% were obese. There was a high prevalence of hypertension and prehypertension, at 17.1% and 48.8%, respectively. Among hypertensive people, most had uncontrolled hypertension, at 97.4%. When we examined associated factors, older age (adjusted prevalence ratio (APR): 3.1, 95% CI: 2.2-4.4, APR: 5.2, 95% CI: 3.7-7.3, APR: 8.9, 95% CI: 6.4-12.5 among 30-44, 45-59, and 60+-year-old people than 18-29-year-olds), alcohol drinking (APR: 1.6, 95% CI: 1.3-2.0, ref: no), always adding salt during eating (APR: 1.6, 95% CI: 1.1-2.2, ref: no), poor physical activity (APR: 1.3, 95% CI: 1.1-1.6, ref: no), overweight (APR: 1.3, 95% CI: 1.1-1.5, ref: normal weight), and obesity (APR: 2.0, 95% CI: 1.6-2.4, ref: normal weight) had higher prevalence of hypertension than their counterparts. The high prevalence of NCD risk factors highlights the immediate need to implement and scale-up population-level strategies to increase awareness about leading NCD risk factors in Uganda. These strategies should be accompanied by concomitant investment in building health systems capacity to manage and control NCDs.

Healthy aging meta-analyses and scoping review of risk factors across Latin America reveal large heterogeneity and weak predictive models

Models of healthy aging are typically based on the United States and Europe and may not apply to diverse and heterogeneous populations. In this study, our objectives were to conduct a meta-analysis to assess risk factors of cognition and functional ability across aging populations in Latin America and a scoping review focusing on methodological procedures. Our study design included randomized controlled trials and cohort, case–control and cross-sectional studies using multiple databases, including MEDLINE, the Virtual Health Library and Web of Science. From an initial pool of 455 studies, our meta-analysis included 38 final studies (28 assessing cognition and 10 assessing functional ability, n = 146,000 participants). Our results revealed significant but heterogeneous effects for cognition (odds ratio (OR) = 1.20, P = 0.03, confidence interval (CI) = (1.0127, 1.42); heterogeneity: I2 = 92.1%, CI = (89.8%, 94%)) and functional ability (OR = 1.20, P = 0.01, CI = (1.04, 1.39); I2 = 93.1%, CI = (89.3%, 95.5%)). Specific risk factors had limited effects, especially on functional ability, with moderate impacts for demographics and mental health and marginal effects for health status and social determinants of health. Methodological issues, such as outliers, inter-country differences and publication bias, influenced the results. Overall, we highlight the specific profile of risk factors associated with healthy aging in Latin America. The heterogeneity in results and methodological approaches in studying healthy aging call for greater harmonization and further regional research to understand healthy aging in Latin America.

Impact of hypertensive disorders of pregnancy on offspring cardiovascular function. Study from fetal life to early childhood.

Epidemiological studies suggest that children following in utero exposure to hypertensive disorders of pregnancy (HDP) may be at increased long term cardiovascular risk. However, data in early childhood are lacking. We aimed to investigate the independent influence of HDP on childhood heart after accounting for differences in childhood risk factor profile. We performed detailed cardiovascular assessment in fetuses at mid-gestation and at a median of 2.3 years (IQR: 2.1, 2.4 years) postnatally in 71 cases where the mothers had HDP and 304 who did not have HDP. There were no differences in demographic characteristics between groups but in the HDP group delivery was earlier and birthweight was lower. In fetal life, there were no significant differences in cardiac function or structure between the HDP and non-HDP groups. In early childhood, in the HDP compared to the non-HDP group, there was greater relative wall thickness (0.7 SD 0.3 vs. 0.6 SD 0.3 mm, p=0.047) and increased left ventricular mass (80.9 SD 20.4 vs. 75.7 SD 16.5, p=0.024); however, these differences were abolished following multivariable analysis. Longitudinal analysis revealed that in HDP, compared to the non-HDP group, there was no difference in the change of cardiac functional indices from fetal life to early childhood. Epidemiological studies suggest that HDP have an adverse impact on offspring cardiovascular health, but such an effect is not apparent in fetal life or in early childhood. This article is protected by copyright. All rights reserved.

Risk of recurrent venous thromboembolism and major bleeding according to risk factor profiles in Asian patients: a subgroup analysis EINSTEIN-Extension and EINSTEIN-CHOICE

BackgroundRisks of recurrence and major bleeding with extended anticoagulation in Asian patients with venous thromboembolism (VTE) are similar to those in non-Asian patients but risks according to baseline risk factor profiles is not well documented.MethodsSubgroup analysis of two randomized trials, which compared once-daily rivaroxaban (20 mg or 10 mg) with placebo or aspirin (100 mg) for extended treatment in Asian patients with VTE who had completed 6–12 months of anticoagulation. Index events were classified as unprovoked, provoked by major persistent risk factors, minor persistent risk factors, minor transient risk factors, or major transient risk factors. One-year cumulative risks of recurrent VTE were calculated for these risk factor profiles.Results367 patients received rivaroxaban, 159 aspirin, and 48 placebo. For patients with unprovoked VTE, one-year cumulative incidences of recurrence in the 202 patients given rivaroxaban, the 89 given aspirin and the 28 given placebo were 1.6%, 5.8%, and 14.8%, respectively. For patients with VTE provoked by minor persistent risk factors, these incidences were 0% in the 74 patients given rivaroxaban, 9.3% in the 36 given aspirin, and 0% in the 12 given placebo. No recurrent VTE occurred in patients with VTE provoked by major persistent or transient risk factors or minor transient risk factors. Rivaroxaban was not associated with a significant increase in major bleeding.ConclusionsRivaroxaban seems to be an effective and safe option for extended treatment in Asian patients, especially those presenting with unprovoked VTE. Subgroups of patients with provoked risk factors were too small to draw meaningful conclusions.Trial registrationNCT00439725 and NCT02064439.

Patterns and correlates of mental healthcare utilization during the COVID-19 pandemic among individuals with pre-existing mental disorder.

How did mental healthcare utilization change during the COVID-19 pandemic period among individuals with pre-existing mental disorder? Understanding utilization patterns of these at-risk individuals and identifying those most likely to exhibit increased utilization could improve patient stratification and efficient delivery of mental health services. This study leveraged large-scale electronic health record (EHR) data to describe mental healthcare utilization patterns among individuals with pre-existing mental disorder before and during the COVID-19 pandemic and identify correlates of high mental healthcare utilization. Using EHR data from a large healthcare system in Massachusetts, we identified three "pre-existing mental disorder" groups (PMD) based on having a documented mental disorder diagnosis within the 6 months prior to the March 2020 lockdown, related to: (1) stress-related disorders (e.g., depression, anxiety) (N = 115,849), (2) serious mental illness (e.g., schizophrenia, bipolar disorders) (N = 11,530), or (3) compulsive behavior disorders (e.g., eating disorder, OCD) (N = 5,893). We also identified a "historical comparison" group (HC) for each PMD (N = 113,604, 11,758, and 5,387, respectively) from the previous year (2019). We assessed the monthly number of mental healthcare visits from March 13 to December 31 for PMDs in 2020 and HCs in 2019. Phenome-wide association analyses (PheWAS) were used to identify clinical correlates of high mental healthcare utilization. We found the overall number of mental healthcare visits per patient during the pandemic period in 2020 was 10-12% higher than in 2019. The majority of increased visits was driven by a subset of high mental healthcare utilizers (top decile). PheWAS results indicated that correlates of high utilization (prior mental disorders, chronic pain, insomnia, viral hepatitis C, etc.) were largely similar before and during the pandemic, though several conditions (e.g., back pain) were associated with high utilization only during the pandemic. Limitations included that we were not able to examine other risk factors previously shown to influence mental health during the pandemic (e.g., social support, discrimination) due to lack of social determinants of health information in EHR data. Mental healthcare utilization among patients with pre-existing mental disorder increased overall during the pandemic, likely due to expanded access to telemedicine. Given that clinical correlates of high mental healthcare utilization in a major hospital system were largely similar before and during the COVID-19 pandemic, resource stratification based on known risk factor profiles may aid hospitals in responding to heightened mental healthcare needs during a pandemic.

A Comprehensive Analysis of Clinical, Demographic, Risk Factor, and Echocardiography Profiles of Coronary Slow Flow Phenomenon from Somalia’s Largest PCI Center

A Comprehensive Analysis of Clinical, Demographic, Risk Factor, and Echocardiography Profiles of Coronary Slow Flow Phenomenon from Somalia’s Largest PCI Center

Association of Autoimmune Diseases With Coronary Atherosclerosis Severity and Ischemic Events

BackgroundSome autoimmune diseases carry elevated risk for atherosclerotic cardiovascular disease (ASCVD), yet the underlying mechanism and the influence of traditional risk factors remain unclear. ObjectivesThis study sought to determine whether autoimmune diseases independently correlate with coronary atherosclerosis and ASCVD risk and whether traditional cardiovascular risk factors modulate the risk. MethodsThe study included 85,512 patients from the Western Denmark Heart Registry undergoing coronary computed tomography angiography. A diagnosis of 1 of 18 autoimmune diseases was assessed. Adjusted OR (aOR) for any plaque, any coronary artery calcification (CAC), CAC of >90th percentile, and obstructive coronary artery disease as well as adjusted HR (aHR) for ASCVD were calculated. ResultsDuring 5.3 years (Q1-Q3: 2.8-8.2 years) of follow-up, 3,832 ASCVD events occurred. A total of 4,064 patients had a diagnosis of autoimmune disease, which was associated with both presence of any plaque (aOR: 1.29; 95% CI: 1.20-1.40), any CAC (aOR: 1.28; 95% CI: 1.19-1.37), and severe CAC of >90th percentile (aOR: 1.53; 95% CI: 1.39-1.68), but not with having obstructive coronary artery disease (aOR: 1.04; 95% CI: 0.91-1.17). Patients with autoimmune diseases had a 46% higher risk (aHR: 1.46; 95% CI: 1.29-1.65) for ASCVD. Traditional cardiovascular risk factors were strongly associated with future ASCVD events, and a favorable cardiovascular risk factor profile in autoimmune patients was associated with ∼54% lower risk compared to patients with presence of risk factors (aHR: 0.46; 95% CI: 0.27-0.81). ConclusionsAutoimmune diseases were independently associated with higher burden of coronary atherosclerosis and higher risk for future ASCVD events, with risk accentuated by traditional cardiovascular risk factors. These findings suggest that autoimmune diseases increase risk through accelerated atherogenesis and that cardiovascular risk factor control is key for improving prognosis in patients with autoimmune diseases.

Stroke and stroke prevention in cardiac and thoracic aortic surgery

Perioperative stroke and neurological injuries in general are complications that can occur during and after cardiac surgery, particularly in aortic surgery that involves the aortic arch. The overall incidence of early and delayed stroke is about 1% according to recent meta-analyses. This incidence depends on interindividual risk factor profile and type of surgery. In order to reduce cerebrovascular complications during cardiac surgery, a number of preventative measures can be taken, including the evaluation of atherosclerotic plaques, the site of cannulation and neuroprotection strategies. During aortic arch surgery, main strategies for cerebral protection are represented by deep hypothermic circulatory arrest, retrograde and antegrade cerebral perfusion.

Cardiotoxicity from bruton tyrosine kinase inhibitors (BTKi)—an analysis of an administrative health claims database

BackgroundFirst generation Bruton tyrosine kinase inhibitors (BTKi) such as ibrutinib have been associated with cardiovascular toxicities. Newer generation BTKi (e.g.,acalabrutinib and zanabrutinib) have been associated with lower incidence of cardiotoxicity in clinical trials.ObjectiveGiven paucity in real-world data on the overall cardiac risk factor profile, especially with the newer BTKi, our study evaluated the incidence of cardiotoxicity with various BTKi among a large, commercially insured population of patients.MethodsWe performed a retrospective cohort analysis of all adults with a diagnosis of B-cell malignancy undergoing treatment with BTKi acalabrutinib and ibrutinib between January 2018 and June 2020 using Optum’s de-identified Clinformatics® Data Mart Database. We then identified patients who had pre-existing cardiac disease one year prior to starting BTKi. New incidence of atrial fibrillation/flutter, hypertension, bleeding, ventricular tachycardia/fibrillation and sudden cardiac death from the time of index presciption were compared with standard Chi Square or Student t-test where appropriate. Multivariate logistic regression models were also estimated to evaluate for confounding.ResultsA total of 1691 patients were included in the final analysis. 1595 (94%, median age 75 (19–90) years, 61% male gender) patients received ibrutinib, and 96 (6%, median age 73.5 (32–90) years, 62.5% male gender) patients received acalabrutinib. The median duration of drug exposure of ibrutinib was 238 (2-1084) days vs. 150 (30–870) days for acalabrutinib. There was lower new incidence of atrial fibrillation/flutter (4.6%-vs-17%, p = 0.013), hypertension (6.3%-vs-25%, p = NS), sudden cardiac arrest/death (0% vs. 1.5%, p = NS) in the acalabrutinib group compared to ibrutinib, of which only the lower incidence of atrial fibrillation/flutter was statistically significant. This was despite the finding of a higher prevalence of atrial fibrillation/flutter at baseline in patients receiving acalabrutinib.ConclusionsThere was lower incidence of new atrial fibrillation/flutter with acalabrutinib when compared to ibrutinib in a real-world cohort of patients.

Specification curve analysis to identify heterogeneity in risk factors for dementia: findings from the UK Biobank

BackgroundIn 2020, the Lancet Commission identified 12 risk factors as priorities for prevention of dementia, and other studies identified APOE e4/e4 genotype and family history of Alzheimer’s disease strongly associated with dementia outcomes; however, it is unclear how robust these relationships are across dementia subtypes and analytic scenarios. Specification curve analysis (SCA) is a new tool to probe how plausible analytical scenarios influence outcomes.MethodsWe evaluated the heterogeneity of odds ratios for 12 risk factors reported from the Lancet 2020 report and two additional strong associated non-modifiable factors (APOE e4/e4 genotype and family history of Alzheimer’s disease) with dementia outcomes across 450,707 UK Biobank participants using SCA with 5357 specifications across dementia subtypes (outcomes) and analytic models (e.g., standard demographic covariates such as age or sex and/or 14 correlated risk factors).ResultsSCA revealed variable dementia risks by subtype and age, with associations for TBI and APOE e4/e4 robust to model specification; in contrast, diabetes showed fluctuating links with dementia subtypes. We found that unattributed dementia participants had similar risk factor profiles to participants with defined subtypes.ConclusionsWe observed heterogeneity in the risk of dementia, and estimates of risk were influenced by the inclusion of a combination of other modifiable risk factors; non-modifiable demographic factors had a minimal role in analytic heterogeneity. Future studies should report multiple plausible analytic scenarios to test the robustness of their association. Considering these combinations of risk factors could be advantageous for the clinical development and evaluation of novel screening models for different types of dementia.

A 10-year review of presentation, management and outcomes of STEMI in a high-volume regional tertiary Australian centre

ObjectiveTo assess the trends and impact of changes in management of ST Elevation Myocardial Infarction (STEMI) from 2010 to 2019. DesignRetrospective analysis of data from STEMI hospitalisations including demographic, comorbidity, angiographic and outcome data. Setting/participantsHigh-volume non-surgical regional Australian tertiary referral centre. Main outcome measurementsIndex & 12-month mortality (all-cause & cardiovascular), door-to-balloon time, target-vessel failure, target-vessel revascularisation & procedure-related bleeding. ResultsFrom 2010 to 2019, 1299 patients presented with STEMI. The cardiovascular risk factor profile did not significantly change over the 10-year study period, p = 0.23. There was a significant trend toward culprit vessel percutaneous coronary intervention with stenting, rather than balloon angioplasty followed by surgical revascularisation, p = 0.029. The mean door-to-balloon time was 88 +/− 5.7 min and demonstrated a statistically significant improvement across the decade, p = 0.035. Radial access became the preferred angiographic approach (2010 92% femoral, 2019 91% radial). Drug-eluting stents (DES) replaced bare metal stent use. There was a statistically significant reduction in 12-month cardiovascular mortality across the decade (p = 0.042). However index hospitalisation (cardiovascular and all-cause) and 12-month all-cause mortality did not reduce. Young patients and women are important sub-groups of STEMI presentations with different risk factor profile. ConclusionsAdvances in management of STEMI such as radial access, use of DES and a significant reduction in door-to-balloon time across the decade resulted in a reduction of 12-month cardiovascular mortality over the decade however there was no significant reduction in 12-month all-cause mortality, or index hospitalisation cardiovascular or index hospitalisation all-cause mortality. Further research is needed to ensure non-mortality outcomes, such as heart failure hospitalisation and quality of life, also demonstrate temporal improvement with STEMI management advances. Earlier cardiovascular risk assessment should be considered in smokers than is currently recommended in Australian guidelines (≥45yo for most individuals).

Cardiovascular safety of dihydroergotamine mesylate delivered by precision olfactory delivery (INP104) for the acute treatment of migraine.

To report the cardiovascular (CV) safety of dihydroergotamine mesylate (DHE) administered by precision olfactory delivery (INP104) from two clinical trials. Although the absolute risk is low, migraine is associated with an increased risk of CV events. DHE is a highly effective acute treatment for migraine, but due to its theoretical risk of promoting arterial vasoconstriction, DHE is contraindicated in patients with CV disease or an unfavorable risk factor profile. The INP104 is a novel drug-device combination product approved for acute treatment of migraine that delivers DHE to the upper nasal space using precision olfactory delivery (POD®). The STOP 101 was a Phase 1 open-label study that assessed the safety, tolerability, and bioavailability of INP104 1.45 mg, intravenous DHE 1.0 mg, and MIGRANAL (nasal DHE) 2.0 mg in healthy participants. The STOP 301 was a pivotal Phase 3, open-label study that assessed the safety, tolerability, and exploratory efficacy of INP104 1.45 mg over 24 and 52 weeks in patients with migraine. In both studies, active or a history of CV disease, as well as significant CV risk factors, were exclusion criteria. In STOP 101, 36 participants received one or more doses of investigational product. Treatment with intravenous DHE, but not INP104 or nasal DHE, resulted in clinically relevant changes from baseline in systolic blood pressure (BP; 11.4 mmHg, 95% confidence interval [CI] 7.9-15.0) and diastolic BP (13.3 mmHg, 95% CI 9.4-17.1) at 5 min post-dose, persisting up to 30 min post-dose for systolic BP (6.3 mmHg; 95% CI 3.0-9.5) and diastolic BP (7.9 mmHg, 95% CI 3.9-11.9). None of the treatments produced any clinically meaningful electrocardiogram (ECG) changes. In STOP 301, 354 patients received one or more doses of INP104. Over 24 weeks, five patients (1.4%) experienced a non-serious, vascular treatment-emergent adverse event (TEAE). Minimal changes were observed for BP and ECG parameters over 24 or 52 weeks. Off-protocol concomitant use of triptans and other ergot derivatives did not result in any TEAEs. In two separate studies, INP104 demonstrated a favorable CV safety profile when used in a study population without CV-related contraindications.